107 results on '"Tatsuya Takenouchi"'
Search Results
2. Systemic therapy for Asian patients with advanced BRAF V600‐mutant melanoma in a real‐world setting: A multi‐center retrospective study in Japan (B‐CHECK‐RWD study)
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Kenjiro Namikawa, Takamichi Ito, Shusuke Yoshikawa, Koji Yoshino, Yukiko Kiniwa, Shuichi Ohe, Taiki Isei, Tatsuya Takenouchi, Hiroshi Kato, Satoru Mizuhashi, Satoshi Fukushima, Yosuke Yamamoto, Takashi Inozume, Yasuhiro Fujisawa, Osamu Yamasaki, Yasuhiro Nakamura, Jun Asai, Takeo Maekawa, Takeru Funakoshi, Shigeto Matsushita, Eiji Nakano, Kohei Oashi, Junji Kato, Hisashi Uhara, Takuya Miyagawa, Hiroshi Uchi, Naohito Hatta, Keita Tsutsui, Taku Maeda, Taisuke Matsuya, Hiroto Yanagisawa, Ikko Muto, Mao Okumura, Dai Ogata, and Naoya Yamazaki
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Asian ,BRAF ,immune‐checkpoint inhibitor ,melanoma ,targeted therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Anti‐PD‐1‐based immunotherapy is considered a preferred first‐line treatment for advanced BRAF V600‐mutant melanoma. However, a recent international multi‐center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non‐acral cutaneous subtype. We hypothesized that the optimal first‐line treatment for Asian patients may be different. Methods We retrospectively collected data of Asian patients with advanced BRAF V600‐mutant melanoma treated with first‐line BRAF/MEK inhibitors (BRAF/MEKi), anti‐PD‐1 monotherapy (Anti‐PD‐1), and nivolumab plus ipilimumab (PD‐1/CTLA‐4) between 2016 and 2021 from 28 institutions in Japan. Results We identified 336 patients treated with BRAF/MEKi (n = 236), Anti‐PD‐1 (n = 64) and PD‐1/CTLA‐4 (n = 36). The median follow‐up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow‐up. For patients treated with BRAF/MEKi, anti‐PD‐1, PD‐1/CTLA‐4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p
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- 2023
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3. Alopecia neoplastica: A manifestation of metastatic breast cancer
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Shohei Kitayama, Koji Katsuumi, Sumiko Takatsuka, Chizuko Kanbayashi, Tadamichi Shimizu, and Tatsuya Takenouchi
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Dermatology ,RL1-803 - Published
- 2023
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4. Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients
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Tatsuhiko Mori, Kenjiro Namikawa, Naoya Yamazaki, Yukiko Kiniwa, Osamu Yamasaki, Shusuke Yoshikawa, Takashi Inozume, Hiroshi Kato, Yasuo Nakai, Satoshi Fukushima, Tatsuya Takenouchi, Takeo Maekawa, Shigeto Matsushita, Atsushi Otsuka, Motoo Nomura, Natsuki Baba, Taiki Isei, Shintaro Saito, Noriki Fujimoto, Ryo Tanaka, Takahide Kaneko, Yutaka Kuwatsuka, Taisuke Matsuya, Kotaro Nagase, Masazumi Onishi, Takehiro Onuma, and Yasuhiro Nakamura
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melanoma ,programmed cell death 1 receptor ,immunotherapy ,salvage therapy ,nails ,Medicine (General) ,R5-920 - Abstract
BackgroundAnti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.Patients and methodsThe study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsThirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p
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- 2023
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5. Treatment outcomes of mucosal melanoma of head and neck: Efficacy of immune checkpoint inhibitors for advanced disease
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Shusuke Ohshima, Yushi Ueki, Yusuke Yokoyama, Takeshi Takahashi, Ryusuke Shodo, Keisuke Yamazaki, Ryuichi Okabe, Hiroshi Matsuyama, Takafumi Togashi, Sumiko Takatsuka, Tatsuya Takenouchi, and Arata Horii
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Head and neck mucosal melanoma ,Advanced disease ,Immune checkpoint inhibitor ,Immune-related adverse events ,Overall Response Rate (ORR) ,Surgery ,RD1-811 - Abstract
BackgroundHead and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM.MethodsCases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated.ResultsThe median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8–54.2 months at the end of the follow-up period.ConclusionsICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.
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- 2022
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6. Systemic melanoma therapy at the end of life: A single institutional retrospective study in Japan
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Ayumi Yoto, MD, Kanade Shimada, MD, Sumiko Takatsuka, MD, and Tatsuya Takenouchi, MD, PhD
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BRAF/MEK inhibitors ,drug treatment ,end of life ,immune checkpoint inhibitors ,melanoma ,terminal stage ,Dermatology ,RL1-803 - Published
- 2023
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7. Less extensive reconstructive surgery for full-thickness lower eyelid defect
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Jin Sasaki, MD, Yu Matsui, MD, Sumiko Takatsuka, MD, and Tatsuya Takenouchi, MD, PhD
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local anesthesia ,less extensive ,reconstruction of the lower eyelid defect ,reconstruction ,skin cancer ,the elderly ,Dermatology ,RL1-803 - Published
- 2021
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8. Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma
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Yasuhiro Fujisawa, Shusuke Yoshikawa, Akane Minagawa, Tatsuya Takenouchi, Kenji Yokota, Hiroshi Uchi, Naoki Noma, Yasuhiro Nakamura, Jun Asai, Junji Kato, Susumu Fujiwara, Satoshi Fukushima, Jiro Uehara, Toshihiko Hoashi, Tatsuya Kaji, Taku Fujimura, Kenjiro Namikawa, Manabu Yoshioka, Naoki Murao, Dai Ogata, Kanako Matsuyama, Naohito Hatta, Yoshitsugu Shibayama, Toshiharu Fujiyama, Masashi Ishikawa, Daisuke Yamada, Akiko Kishi, Yoshiyuki Nakamura, Takatoshi Shimiauchi, Kazuyasu Fujii, Manabu Fujimoto, Hironobu Ihn, and Norito Katoh
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acral ,Asian ,Epidemiology ,Japanese ,Melanoma ,mucosal ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large‐scale Asian studies that include follow‐up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan‐Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease‐specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5‐year disease‐specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5‐year disease‐specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.
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- 2019
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9. Analyzing the relationship between the efficacy of first-line immune checkpoint inhibitors and cumulative sun damage in Japanese patients with advanced BRAF wild-type nonacral cutaneous melanoma: A retrospective real-world, multicenter study
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Takashi Inozume, Kenjiro Namikawa, Hiroshi Kato, Shusuke Yoshikawa, Yukiko Kiniwa, Koji Yoshino, Satoru Mizuhashi, Takamichi Ito, Tatsuya Takenouchi, Shigeto Matsushita, Yasuhiro Fujisawa, Takamitsu Matsuzawa, Satoru Sugihara, Jun Asai, Hiroshi Kitagawa, Takeo Maekawa, Taiki Isei, Masahito Yasuda, Naoya Yamazaki, Hisashi Uhara, and Yasuhiro Nakamura
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Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
10. Efficacy comparison between anti-PD-1 antibody monotherapy and anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy for advanced acral melanoma: A retrospective, multicenter study of 254 Japanese patients
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Yasuhiro Nakamura, Kenjiro Namikawa, Yukiko Kiniwa, Hiroshi Kato, Osamu Yamasaki, Shusuke Yoshikawa, Takeo Maekawa, Shigeto Matsushita, Tatsuya Takenouchi, Takashi Inozume, Yasuo Nakai, Satoshi Fukushima, Shintaro Saito, Atsushi Otsuka, Noriki Fujimoto, Taiki Isei, Natsuki Baba, Taisuke Matsuya, Ryo Tanaka, Takahide Kaneko, Masazumi Onishi, Yutaka Kuwatsuka, Kotaro Nagase, Takehiro Onuma, Motoo Nomura, Yoshiyasu Umeda, and Naoya Yamazaki
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Cancer Research ,Japan ,Oncology ,Programmed Cell Death 1 Receptor ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Immunologic Factors ,Immunotherapy ,Ipilimumab ,Melanoma ,Retrospective Studies - Abstract
Although anti-PD-1 antibody monotherapy (PD-1) is commonly used to treat advanced acral melanoma (AM), its efficacy is limited. Further, data on the efficacy of PD-1 plus anti-CTLA-4 antibody (PD-1+CTLA-4) for the treatment of AM are limited. Therefore, we compared the efficacy of PD-1+CTLA-4 and PD-1 in the treatment of Japanese patients with advanced AM.This retrospective study evaluated patients with advanced AM who were treated with PD-1 or PD-1+CTLA-4 as first-line immunotherapy in 24 Japanese institutions between 2014 and 2020. Treatment efficacy focussing on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was compared between the two groups.In total, 254 patients (palm and sole melanoma [PSM], n = 180; nail apparatus melanoma [NAM], n = 74) were included. Among the patients with PSM, the ORR (19% vs. 31%; P = 0.44), PFS (5.9 vs. 3.2 months; P = 0.74), and OS (23.1 vs. not reached; P = 0.55) did not differ significantly between the PD-1 and PD-1+CTLA-4 groups. Among the patients with NAM, the ORR (61% vs. 10%; P 0.001) was significantly higher and PFS was longer (6.4 vs. 3.8 months; P = 0.10) in the PD-1+CTLA-4 group than in the PD-1 group. Cox multivariate analysis demonstrated that PD-1+CTLA-4 is an independent predictor of a favourable PFS in patients with NAM (P = 0.002).The efficacy of PD-1+CTLA-4 is not superior to that of PD-1 for the treatment of advanced PSM. However, PD-1+CTLA-4 may be more efficacious than PD-1 for the treatment of advanced NAM.
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- 2022
11. A phase I study of the safety and efficacy of talimogene laherparepvec in Japanese patients with advanced melanoma
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Naoya Yamazaki, Taiki Isei, Yoshio Kiyohara, Hiroshi Koga, Takashi Kojima, Tatsuya Takenouchi, Kenji Yokota, Kenjiro Namikawa, Min Yi, Alissa Keegan, and Satoshi Fukushima
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Adult ,Male ,Oncolytic Virotherapy ,Biological Products ,Cancer Research ,Skin Neoplasms ,Japan ,Oncology ,Humans ,Female ,Herpesvirus 1, Human ,General Medicine ,Melanoma - Abstract
Talimogene laherparepvec (T-VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open-label, dose de-escalation study evaluated the safety and efficacy of T-VEC in Japanese patients with unresectable stage IIIB-IV melanoma. Eligible adult patients had histologically confirmed stage IIIB-IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T-VEC was injected intralesionally (first dose, ≤4.0 ml of 10
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- 2022
12. Combined use of nivolumab and ipilimumab among Japanese melanoma patients: Multi-center, retrospective study of 111 cases
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Yasuhiro Fujisawa, Kenjiro Namikawa, Koji Yoshino, Yukiko Kiniwa, Takamichi Ito, Hiroshi Kato, Shigeto Matsushita, Toshihiko Hoashi, Yasuhiro Nakamura, Shusuke Yoshikawa, Takuya Miyagawa, Jun Asai, Taisuke Matsuya, Satoshi Fukushima, Jyunji Kato, Tatsuya Takenouchi, Hiroshi Uchi, Mamiko Masuzawa, Teruki Yanagi, and Takeo Maekawa
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Dermatology - Abstract
In Japanese melanoma patients, the response rate of N/I was lower (35.1%) and the rate of adverse events was similar (60.4%) compared to those reported in previous clinical trials. No survival difference was observed with the use of N/I between clinical types. Patients who achieved a good response had better outcomes. Elevated LDH level and ≥3 metastatic sites were poor prognostic factors.
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- 2023
13. Topical corticosteroid therapy for facial acneiform eruption due to EGFR inhibitors in metastatic colorectal cancer patients: a randomized controlled trial comparing starting with a very strong or a weak topical corticosteroid (FAEISS study, NCCH1512, colorectal part)
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Haruhiko Fukuda, Akiko Hasegawa, Hitoshi Mizutani, Hirokazu Shoji, Tatsuya Takenouchi, Tetsuya Hamaguchi, Taro Shibata, Naoya Yamazaki, Tomohiro Nishina, Keiko Nozawa, Atsuo Takashima, Toshiki Masuishi, Narikazu Boku, Shusuke Yoshikawa, Akihito Kawazoe, Sumiko Takatsuka, Ryunosuke Machida, Yoshio Kiyohara, Katsuko Kikuchi, and Masanobu Takahashi
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medicine.medical_specialty ,Topical Corticosteroid Therapy ,business.industry ,Colorectal cancer ,Cetuximab ,medicine.disease ,Acneiform eruption ,Dermatology ,law.invention ,ErbB Receptors ,Topical corticosteroid ,Randomized controlled trial ,Acneiform Eruptions ,Oncology ,law ,Colonic Neoplasms ,medicine ,Quality of Life ,Humans ,medicine.symptom ,business ,Colorectal Neoplasms ,Glucocorticoids ,EGFR inhibitors - Abstract
Background: Althoughpre-emptive therapy with oral tetracycline, moisturizer, sunscreen and topical corticosteroid isuseful for preventing acneiform eruption (AfE) due to epidermal growth factor receptor (EGFR) inhibitors, no studies have examinedthe efficacy of topical corticosteroids themselves, or investigated the optimal strength of the corticosteroid for treating facial AfE (FAfE).Patients and Methods: Screened patients with RAS wild-typecolorectal cancerstarted pre-emptive therapy with oral minocycline and moisturizeron initiation of cetuximab or panitumumab therapy. Patients who developed grade 1 or 2 FAfEwere randomly allocated to two groups:a ranking-down (RD) group,started with a very strong corticosteroid, and serially ranked down every 2 weeks unless FAfE exacerbated, and a ranking-up (RU) group, started with a weak corticosteroid and serially ranked up at exacerbation. FAfE grade, patient quality of life, and adverse events (AEs) with topical corticosteroid were evaluated every 2 weeks.The primary endpoint was the total number of times grade 2 or higher FAfEidentified in thecentral review of the 8-weektreatment period.Results: No significant differences in total numbers of grade 2 or higher FAfE and inAEs caused by topical corticosteroids were observedbetweengroups during the 8-week. Incidence of grade 2 or higher FAfEwas tended to lower inthe RD group during the first 2 weeks.Conclusion: Considering long-term care of FAfE, the RU regimen appears suitableand should be considered the standard treatment for FAfEdue to EGFR inhibitor therapy. Trial registration: UMIN Clinical Trials Registry (UMIN000024113)
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- 2022
14. Natural course of pediatric longitudinal melanonychia: A retrospective cohort study in Japan
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Yu Matsui, Sumiko Takatsuka, Jin Sasaki, and Tatsuya Takenouchi
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Nevus, Pigmented ,Pediatrics ,medicine.medical_specialty ,Natural course ,Skin Neoplasms ,business.industry ,Retrospective cohort study ,Dermatology ,Nail Diseases ,Japan ,Melanonychia striata ,medicine ,Humans ,Child ,business ,Longitudinal melanonychia ,Retrospective Studies - Published
- 2022
15. Observation policy for sentinel node metastasis of melanoma: Comparative study with completion lymph node dissection in Japanese patients
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Tatsuya Takenouchi, Yu Matsui, Jin Sasaki, and Sumiko Takatsuka
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medicine.medical_specialty ,Skin Neoplasms ,Dermatology ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Randomized controlled trial ,law ,medicine ,Adjuvant therapy ,Humans ,Melanoma ,Lymph node ,Retrospective Studies ,Sentinel Lymph Node Biopsy ,business.industry ,Cancer ,General Medicine ,Sentinel node ,medicine.disease ,Dissection ,Policy ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Lymph Node Excision ,Lymph ,Radiology ,Neoplasm Recurrence, Local ,Sentinel Lymph Node ,business - Abstract
Based on the results of international multicenter randomized trials, completion lymph node dissection for patients with sentinel lymph node-positive melanoma is no longer routinely recommended. However, clinicians should take into consideration racial and medical resource differences when applying this evidence to clinical practice in Japan. To evaluate the clinical validity of the observation policy of omitting completion lymph node dissection, we retrospectively surveyed patients with sentinel lymph node-positive melanoma between 2002 and 2020 at Niigata Cancer Center Hospital. A total of 59 patients were categorized into the observation group (n = 19) and completion lymph node dissection group (n = 40). Newly developed anticancer agents, including targeted therapy and immunotherapy, were more commonly used in the observation group than in the completion lymph node dissection group as either adjuvant therapy (31.6% vs. 5.0%) or post-recurrence therapy (100% vs. 34.8%). The median overall survival in the observation group (not reached) was significantly longer than that in the completion lymph node dissection group (95.0 months; p = 0.02), which was mainly attributed to the difference in post-recurrence overall survival. There was no significant difference in recurrence-free survival between the two groups (p = 0.63). Although the use of new anticancer agents leads to bias, this study demonstrates that observation without prompt completion lymph node dissection provides a favorable overall survival without increasing the risk of recurrence compared with completion lymph node dissection. The observation policy for patients with sentinel lymph node-positive melanoma patients is considered to be clinically valid in real-world medical practice.
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- 2021
16. Five‐year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma
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Tatsuya Takenouchi, Naoya Yamazaki, Hiroshi Uchi, Yasuhiro Fujisawa, Hisashi Uhara, Jiro Uehara, Yoshio Kiyohara, Masahiro Hatsumichi, Hironobu Minami, Satoshi Fukushima, and Masaki Otsuka
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medicine.medical_specialty ,Skin Neoplasms ,Anemia ,Population ,Phases of clinical research ,Dermatology ,survival ,Gastroenterology ,Disease-Free Survival ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,melanoma ,medicine ,Humans ,Adverse effect ,education ,Survival rate ,nivolumab ,education.field_of_study ,business.industry ,long‐term survivors ,Melanoma ,Original Articles ,General Medicine ,medicine.disease ,Ipilimumab ,Progression-Free Survival ,030220 oncology & carcinogenesis ,Original Article ,Nivolumab ,business ,Progressive disease - Abstract
We report the 5‐year follow‐up results from a single‐arm, open‐label, multicenter phase II study (ONO‐4538‐08) conducted in Japan. Twenty‐four patients with treatment‐naïve, recurrent, or unresectable stage III/IV malignant melanoma received 3 mg/kg nivolumab every 2 weeks until progressive disease or unacceptable toxicity occurred. The 5‐year overall survival (OS) rate was 26.1%. Five years after the start of nivolumab treatment, there were six survivors. The 5‐year OS rate was 66.7% for patients with a superficial spreading type, 14.3% for acral lentiginous type, and 16.7% for mucosal type. The 5‐year progression‐free survival rate was 17.2%. No new cases of partial response or complete response were observed after 3 years, and overall response and disease control rates were similar to those reported at 3 years. The treatment‐related adverse events reported between the 3‐ and 5‐year follow‐up periods were anemia (grade 2), white blood cell count decrease (grade 2), and psoriasiform dermatitis (grade 2) in one patient each. No new grade 3 or higher treatment‐related adverse events occurred in this period. In conclusion, first‐line treatment with nivolumab in Japanese patients with unresectable or metastatic melanoma resulted in confirmed long‐term survival. No new safety signals were reported in the studied population.
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- 2021
17. Risk factors for lymph node metastasis in cutaneous squamous cell carcinoma: a long-term retrospective study of Japanese patients
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Tatsuya Takenouchi, Riichiro Abe, Hiroki Fujikawa, Sumiko Takatsuka, and Yuki Saito
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Skin Neoplasms ,Disease ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Risk Factors ,Infiltrative Growth Pattern ,Surgical oncology ,Internal medicine ,Carcinoma ,medicine ,Humans ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Hazard ratio ,Cancer ,Retrospective cohort study ,Hematology ,General Medicine ,Prognosis ,medicine.disease ,030104 developmental biology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,Surgery ,Lymph Nodes ,business - Abstract
Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers. Prognosis is favorable following surgical resection of early-stage disease, but the management of the metastatic disease is challenging. Several prognostic risk factors have been described in the American Joint Committee on Cancer/the Union for International Cancer Control (UICC) 8th edition staging and the Brigham and Women's Hospital T classification system. However, their clinical validity in Asian populations is unclear because of racial differences in the clinical characteristics of CSCC. This study aimed to identify factors that could predict lymph node metastasis in Asian patients.This retrospective single-center study evaluated 540 patients with primary CSCC between 1989 and 2013. Five factors were evaluated for their ability to predict lymph node metastasis: maximum tumor diameter, tumor thickness, depth of invasion, degree of differentiation, and infiltrative growth pattern (INF).Tumor diameter 2 cm (p 0.0001), tumor thickness 6 mm (p 0.0001), invasion beyond the subcutaneous fat (p 0.0001), poor differentiation (p = 0.042), and INFc infiltration (p 0.0001) were associated with lymph node metastasis in the univariate analyses. In the multivariate analysis, lymph node metastasis was independently associated with tumor size 2 cm [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.4-6.2; p = 0.006], tumor thickness 6.0 mm (HR 2.9, 95% CI 1.3-6.4; p = 0.007), and invasion beyond the subcutaneous fat (HR 2.3, 95% CI 1.0-5.1; p = 0.045).Larger tumor diameter, greater tumor thickness, and deeper invasion included in the UICC T classification system are associated with increased risks of lymph node metastasis from CSCC in Japanese patients.
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- 2020
18. Concordance in judgment of clinical borders of basal cell carcinomas in Japanese patients: A preliminary study of JCOG2005 (J-BASE-MARGIN)
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Anna Kamimura, Yasuhiro Nakamura, Tatsuya Takenouchi, Shigeto Matsushita, Toshikazu Omodaka, Kentaro Yamamura, Hiroshi Uchi, Shusuke Yoshikawa, Hiroto Yanagisawa, Takamichi Ito, Yoshio Kiyohara, Yoshio Nakamura, Megumi Aoki, Shoichiro Ishizuki, Kohei Oashi, Takuya Miyagawa, Taku Maeda, Dai Ogata, Naohito Hatta, Shuichi Ohe, Taiki Isei, Akira Takahashi, Yoshiyasu Umeda, Buntaro Yamaguchi, Masashi Ishikawa, Kohei Horimoto, Yasuhiro Fujsawa, Jiro Uehara, Yoshitsugu Shibayama, Yukiko Kiniwa, Yu Kawahara, Taisuke Matsuya, Hisashi Uhara, Junji Kato, Yoshiyuki Nakamura, Takuo Murakami, Kenjiro Namikawa, Koji Yoshino, Takeru Funakoshi, Sumiko Takatsuka, Yu Matsui, Jin Sasaki, Hiroshi Koga, Kenji Yokota, Takaya Komori, Satoshi Fukushima, and Naoya Yamazaki
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Judgment ,Skin Neoplasms ,Japan ,Carcinoma, Basal Cell ,Head and Neck Neoplasms ,Humans ,Margins of Excision ,Dermatology ,General Medicine - Abstract
Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.
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- 2022
19. Prognoses of patients with melanoma who continue/discontinue anti-programmed death-1 therapy after achieving a complete response in a real-world setting: a multicentre retrospective study
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Junji Kato, Kenjiro Namikawa, Jiro Uehara, Motoo Nomura, Yasuhiro Nakamura, Hisashi Uhara, Hiroshi Uchi, Shusuke Yoshikawa, Yukiko Kiniwa, Yoshiyuki Nakamura, Takuya Miyagawa, Shigeto Matsushita, Tatsuya Takenouchi, Naohito Hatta, Fumitaka Ohno, Taku Maeda, Satoshi Fukushima, and Naoya Yamazaki
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Humans ,Dermatology ,Syndrome ,Prognosis ,Melanoma ,Retrospective Studies - Published
- 2022
20. Less extensive reconstructive surgery for full-thickness lower eyelid defect
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Tatsuya Takenouchi, Sumiko Takatsuka, Jin Sasaki, and Yu Matsui
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medicine.medical_specialty ,Reconstructive surgery ,reconstruction ,Case Report ,Dermatology ,reconstruction of the lower eyelid defect ,medicine ,Tarsal plate ,less extensive ,Local anesthesia ,Basal cell carcinoma ,the elderly ,Eyelid defect ,skin cancer ,business.industry ,medicine.disease ,eye diseases ,Surgery ,body regions ,medicine.anatomical_structure ,RL1-803 ,Full thickness ,sense organs ,Eyelid ,Skin cancer ,local anesthesia ,business - Abstract
The incidence of skin cancers is on the rise due to population growth and aging.1 The eyelid region is one of the common sites for skin cancers, the majority of which are basal cell carcinoma, followed by squamous cell carcinoma and sebaceous carcinoma.2 Of note, the lower eyelid is more prone to be affected by skin cancers. The eyelid is composed of anterior and posterior lamellae, and when full-thickness lower eyelid defects cannot be directly closed, reconstruction of both the posterior and anterior lamellae, along with tarsal plate replacement, are typically performed.3 However, elderly patients with skin cancer may not be amenable to such extensive surgery. Between 1997 and 2019 at our hospital, 5 patients underwent successful reconstruction of full-thickness lower eyelid defects with the repair of only the anterior lamella while allowing the posterior lamellar portion to heal secondarily. We herein report one representative case. In addition, we discuss the clinical validity of less extensive surgery for elderly patients by allowing the posterior lamellar portions of lower eyelid defects to heal secondarily.
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- 2021
21. Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Japanese subgroup analysis from the phase 3 CheckMate 238 study
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Hiroshi Uchi, Tatsuya Takenouchi, Hisashi Uhara, Yasushi Otsuka, Kenji Yokota, Naoya Yamazaki, Veerle de Pril, Anila Qureshi, Takashi Inozume, Hironobu Ihn, Jeffrey S. Weber, Shusuke Yoshikawa, Kentaro Ozawa, and Yasuhiro Fujisawa
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Skin Neoplasms ,Concise Communications ,Subgroup analysis ,Ipilimumab ,Dermatology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Asian People ,Internal medicine ,Adjuvant therapy ,melanoma ,Medicine ,Humans ,Stage (cooking) ,Aged ,nivolumab ,Aged, 80 and over ,business.industry ,Melanoma ,Hazard ratio ,Concise Communication ,General Medicine ,Middle Aged ,medicine.disease ,Confidence interval ,adjuvant drug therapy ,Japanese patients ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,Nivolumab ,business ,medicine.drug - Abstract
The multinational phase 3 CheckMate 238 trial compared adjuvant therapy with nivolumab versus ipilimumab among patients with resected stage III or IV melanoma (N = 906). In this Japanese subgroup analysis of CheckMate 238 (n = 28; nivolumab, n = 18; ipilimumab, n = 10), both the 12‐ and 18‐month recurrence‐free survival rates were 56% for nivolumab and 30% for ipilimumab (hazard ratio, 0.66; 97.56% confidence interval, 0.19–2.24; P = 0.4390). No new safety signals were reported for Japanese patients. Results were consistent with those from the CheckMate 238 global population, indicating that nivolumab has the potential to be a treatment option for Japanese patients with resected melanoma who are at high risk of recurrence.
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- 2019
22. Dermatologist’s role in a cancer hospital: An overview of in‐hospital consultations
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Jin Sasaki, Yu Matsui, Tatsuya Takenouchi, and Sumiko Takatsuka
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medicine.medical_specialty ,medicine.medical_treatment ,Dermatology ,Cancer Care Facilities ,Skin Diseases ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Neoplasms ,medicine ,Humans ,Adverse effect ,Lung cancer ,Referral and Consultation ,Chemotherapy ,business.industry ,Treatment process ,Cancer ,General Medicine ,medicine.disease ,Confidence interval ,030220 oncology & carcinogenesis ,Cancer management ,Quality of Life ,business ,Dermatologists - Abstract
As cancer treatment advances, the need for dermatologists in the treatment process is increasing. Cancer patients often experience cutaneous manifestations of internal diseases and dermatological adverse events from chemotherapy, radiation, surgery, and stem cell transplants. These diminish patients' health-related quality of life and negatively affect cancer treatment adherence. To identify the dermatologist's role, we analyzed 893 cases of in-hospital dermatology consultations at the Niigata Cancer Center Hospital during 2019. The number of dermatology consultations was the second highest among all hospital departments. Malignant tumors accounted for 91.7% of the underlying diseases, including hematological, gastrointestinal, and lung cancer as the top three primary cancers. The most common consultation category was inflammatory skin disorders (29.2%), followed by chemotherapy-related skin disorders (23.5%), cutaneous infections (11.5%), skin tumors (9.5%), and continued treatment of pre-existing skin disorders (8.8%). The average intervention time was the longest for continued treatment of existing skin disorders (229 ± 60.6 days), followed by malignant wound management (126 ± 60.6 days) and chemotherapy-related skin disorders (122 ± 60.6 days). The median overall survival time of the 27 patients in the malignant wound management group was 5 months (95% confidence interval, 1.8-8.2 months) from the initial dermatology consultation. Our results show an increasing demand for dermatologists in cancer management. However, the number of full-time dermatologists is insufficient in some Japanese cancer hospitals. There is a need to consider increasing the number of adequately trained dermatologists in cancer medical settings.
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- 2021
23. Real-world efficacy of anti-PD-1 antibody or combined anti-PD-1 plus anti-CTLA-4 antibodies, with or without radiotherapy, in advanced mucosal melanoma patients: A retrospective, multicenter study
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Takeo Maekawa, Satoshi Fukushima, Taiki Isei, Takehiro Onuma, Naoya Yamazaki, Takashi Inozume, Natsuki Baba, Hiroshi Kato, Osamu Yamasaki, Yasuo Nakai, Yoshiyasu Umeda, Shusuke Yoshikawa, Kotaro Nagase, Taisuke Matsuya, Shigeto Matsushita, Atsushi Otsuka, Takahide Kaneko, Motoo Nomura, Masazumi Onishi, Yasuhiro Nakamura, Yutaka Kuwatsuka, Noriki Fujimoto, Kenjiro Namikawa, Tatsuya Takenouchi, Yukiko Kiniwa, Shintaro Saito, and Ryo Tanaka
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Combination therapy ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Ipilimumab ,Pembrolizumab ,Kaplan-Meier Estimate ,Gastroenterology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,CTLA-4 Antigen ,Survival rate ,Immune Checkpoint Inhibitors ,Melanoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Mucous Membrane ,business.industry ,Mucosal melanoma ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Radiation therapy ,Oncology ,Head and Neck Neoplasms ,Cohort ,Female ,Nivolumab ,business ,medicine.drug - Abstract
Background Immune checkpoint inhibitors (ICIs) have a lower efficacy in mucosal melanoma (MUM) than in cutaneous melanoma. The use of combination treatments with radiotherapy (RT) to improve the efficacy in MUM, however, requires further investigation. Methods We retrospectively evaluated 225 advanced MUM patients treated with anti-PD-1 monotherapy (PD1; 115) or anti-PD-1 + anti-CTLA-4 combination therapy (PD1+CTLA4; 42) with or without RT (56 and 12, respectively). Treatment efficacy was estimated by determining the objective response rate (ORR) and survival rate with the Kaplan–Meier analysis. Results The baseline characteristics between the two groups in each ICI cohort were similar, except for Eastern Cooperative Oncology Group performance status in the PD1 cohort. No significant differences in ORR, progression-free survival (PFS), and overall survival (OS) were observed between the PD1 alone and PD1+RT groups in the PD1 cohort (ORR 26% versus 27%, P > 0.99; median PFS 6.2 versus 6.8 months, P = 0.63; median OS 19.2 versus 23.1 months, P = 0.70) or between the PD1+CTLA alone and PD1+CTLA4+RT groups in the PD1+CTLA4 cohort (ORR 28% vs 25%, P = 0.62; median PFS 5.8 versus 3.5 months, P = 0.21; median OS 31.7 versus 19.8 months, P = 0.79). Cox multivariate analysis indicated that RT in addition to PD1 or PD1+CTLA4 did not have a positive impact on the PFS or OS. Conclusions A prolonged survival benefit with RT in combination with ICIs was not identified for advanced MUM patients, although RT may improve local control of the tumour and relieve local symptoms.
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- 2021
24. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial
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Christoph Hoeller, Marie-Francoise Avril, Pietro Quaglino, François Aubin, Lars Bastholt, Takashi Inozume, Virginia Ferraresi, Michael B. Jameson, Kevin B. Kim, Oliver Bechter, Dirk Schadendorf, Kenji Yokota, Carmen Loquai, Maria-Jose Passos, Inge Marie Svane, Michele Maio, Catherine Barrow, Frank Meiss, Nageatte Ibrahim, Andrzej Mackiewicz, Phillip Parente, Tatsuya Takenouchi, Caroline Dutriaux, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Paola Queirolo, Catriona M. McNeil, Peter Mohr, Felix Kiecker, Susana Puig, Friedegund Meier, Lutz Kretschmer, Alexander C.J. van Akkooi, Alex Menzies, Timothy Crook, Christian U. Blank, Suzana Matkovic, Michael C. Brown, Ragini R. Kudchadkar, Max Levin, Rüdiger Hein, Tanja Skytta, Gerald P. Linette, Clemens Krepler, Adnan Khattak, Ernest Marshall, Joseph Kerger, Oddbjorn Straume, Laurent Mortier, Jochen Utikal, Micaela Hernberg, James Larkin, Yoshio Kiyohara, Mario Mandalà, Henrik Schmidt, Daniil Stroyakovskiy, Pablo Luis Ortiz Romero, Naoya Yamazaki, John Walker, Anna Maria Di Giacomo, Lionel Geoffrois, Jean-Philippe Lacour, Caroline Robert, Vincent Descamps, Shahneen Sandhu, Gil Bar-Sela, Paul C. Nathan, Marcin Dzienis, Ralf Gutzmer, Claus Garbe, Andrey Meshcheryakov, Patrick Combemale, Martin Fehr, Guzel Mukhametshina, Helena Kapiteijn, Geke A. P. Hospers, Jun Aoi, Andrew Haydon, Rutger H. T. Koornstra, Marie-Thérèse Leccia, Sigrun Hallmeyer, Pier Francesco Ferrucci, Jean-Jacques Grob, Leonel Hernandez-Aya, Jan-Christoph Simon, Vanna Chiarion Sileni, Alain Algazi, Lidija Sekulovic, Sandrine Marreaud, Bernard Fitzharris, Jacob Schachter, Xinni Song, Wolf-Henning Boehncke, Rahima Jamal, Paul Lorigan, Maureen J.B. Aarts, Reinhard Dummer, Mike McCrystal, César Martins, Reiner Hofmann-Wellenhof, Alexander M.M. Eggermont, Carola Berking, Elaine Dunwoodie, Bernard Guillot, Michal Kicinski, Philippe Saiag, Céleste Lebbé, Thierry Lesimple, Stefan Suciu, Michal Lotem, Paula Ferreira, Mohammed M. Milhem, Laurent Machet, Patrick Terheyden, Anna Katharina Winge-Main, Peter Hersey, Jean-Francois Baurain, Axel Hauschild, Stéphane Dalle, Jean-Philippe Arnault, Paolo A. Ascierto, Gerard Groenewegen, Florent Grange, Georgina V. Long, Victoria Atkinson, Philippa Corrie, Matteo S. Carlino, Thomas Jouary, Daniel Hendler, Richard Casasola, Ashita Waterston, Jessica C. Hassel, University Medical Center [Utrecht], Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], The University of Sydney, Princess Alexandra Hospital, Brisbane, University of Queensland [Brisbane], Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), N.N. Blokhin National Medical Research Center of Oncology, Edith Cowan University (ECU), Royal Marsden NHS Foundation Trust, Universitat de Barcelona (UB), Instituto de Salud Carlos III [Madrid] (ISC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Radboud University Medical Center [Nijmegen], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University Hospital of Siena, Amsterdam UMC - Amsterdam University Medical Center, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Merck & Co. Inc, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Internal medicine, and CCA - Cancer Treatment and quality of life
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Male ,Skin Neoplasms ,Medizin ,Pembrolizumab ,law.invention ,Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2] ,MESH: Aged, 80 and over ,0302 clinical medicine ,Randomized controlled trial ,law ,Monoclonal ,80 and over ,MESH: Double-Blind Method ,030212 general & internal medicine ,Neoplasm Metastasis ,Humanized ,Melanoma ,MESH: Aged ,Aged, 80 and over ,education.field_of_study ,MESH: Middle Aged ,Hazard ratio ,MESH: Neoplasm Staging ,Middle Aged ,Oncology ,030220 oncology & carcinogenesis ,Female ,Adult ,Aged ,Antibodies, Monoclonal, Humanized ,Double-Blind Method ,Humans ,Neoplasm Staging ,medicine.medical_specialty ,MESH: Melanoma ,Population ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Placebo ,Antibodies ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Internal medicine ,medicine ,Adjuvant therapy ,education ,Cancer staging ,MESH: Humans ,business.industry ,MESH: Skin Neoplasms ,MESH: Adult ,MESH: Neoplasm Metastasis ,MESH: Male ,Clinical trial ,MESH: Antibodies, Monoclonal, Humanized ,business ,MESH: Female - Abstract
Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p
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- 2021
25. Management of Adverse Events Induced by Immune Checkpoint Inhibitors in Lung Cancer Treatment
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Nagayuki Tani, Takasue Kajiwara, Satoru Miura, Hiroshi Tanaka, Masaki Yoshino, Sachiko Isogai, Kenichi Koyama, Junko Baba, and Tatsuya Takenouchi
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Pulmonary and Respiratory Medicine ,Oncology ,business.industry ,Immune checkpoint inhibitors ,Cancer research ,Medicine ,business ,Adverse effect ,Lung cancer ,medicine.disease - Published
- 2019
26. Long-term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma
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Masahiro Hatsumichi, Yasuhiro Fujisawa, Naoya Yamazaki, Tatsuya Takenouchi, Hiroshi Uchi, Hisashi Uhara, Hironobu Minami, Masaki Otsuka, Hironobu Ihn, Yoshio Kiyohara, and Jiro Uehara
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Male ,0301 basic medicine ,survival rate ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,Vitiligo ,malignant melanoma ,Phases of clinical research ,Subgroup analysis ,Kaplan-Meier Estimate ,Gastroenterology ,03 medical and health sciences ,clinical efficacy ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Asian People ,Japan ,Clinical Research ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Melanoma ,Survival rate ,Aged ,nivolumab ,business.industry ,Pruritus ,Original Articles ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,Oncology ,Tolerability ,030220 oncology & carcinogenesis ,Original Article ,Administration, Intravenous ,Neoplasm Recurrence, Local ,Nivolumab ,business ,Follow-Up Studies - Abstract
The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long‐term follow up of a single‐arm, open‐label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post–hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression‐free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment‐related adverse events (TRAE), including select immune‐related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3‐year OS rate was 43.5%, and the 3‐year PFS rate was 17.2%. A long‐term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long‐term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.
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- 2019
27. Classification of 3097 patients from the Japanese melanoma study database using the American joint committee on cancer eighth edition cancer staging system
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Akane Minagawa, Manabu Yoshioka, Akiko Kishi, Naoki Murata, Hiroshi Uchi, Kanako Matsuyama, Tatsuya Kaji, Susumu Fujiwara, Yoshiyuki Nakamura, Kazuyasu Fujii, Manabu Fujimoto, Tatsuya Takenouchi, Shusuke Yoshikawa, Satoshi Fukushima, Norito Katoh, Junji Kato, Naoki Noma, Dai Ogata, Yasuhiro Fujisawa, Yasuhiro Nakamura, Naohito Hatta, Takatoshi Shimiauchi, Masashi Ishikawa, Toshiharu Fujiyama, Daisuke Yamada, Taku Fujimura, Jun Asai, Hironobu Ihn, Toshihiko Hoashi, Kenji Yokota, Kenjiro Namikawa, Yoshitsugu Shibayama, and Jiro Uehara
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0301 basic medicine ,medicine.medical_specialty ,Skin Neoplasms ,Databases, Factual ,Population ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Dermatology ,computer.software_genre ,Biochemistry ,Disease-Free Survival ,Cohort Studies ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Epidemiology ,Humans ,Medicine ,Stage (cooking) ,education ,Melanoma ,Molecular Biology ,Survival analysis ,Neoplasm Staging ,Cancer staging ,education.field_of_study ,Database ,business.industry ,Cancer ,Prognosis ,medicine.disease ,030104 developmental biology ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,Cohort ,Neoplasm Recurrence, Local ,business ,computer - Abstract
Background The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. Objective The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. Methods The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan–Meier method was used to estimate disease-specific survival and relapse-free survival. Results In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. Conclusion The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.
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- 2019
28. Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma
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Taku Fujimura, Tatsuya Kaji, Jun Asai, Norito Katoh, Naoki Noma, Yasuhiro Nakamura, Toshiharu Fujiyama, Naohito Hatta, Kanako Matsuyama, Daisuke Yamada, Takatoshi Shimiauchi, Satoshi Fukushima, Junji Kato, Yasuhiro Fujisawa, Masashi Ishikawa, Hironobu Ihn, Toshihiko Hoashi, Kazuyasu Fujii, Manabu Fujimoto, Naoki Murao, Shusuke Yoshikawa, Dai Ogata, Yoshiyuki Nakamura, Kenjiro Namikawa, Akiko Kishi, Jiro Uehara, Kenji Yokota, Akane Minagawa, Manabu Yoshioka, Susumu Fujiwara, Hiroshi Uchi, Tatsuya Takenouchi, and Yoshitsugu Shibayama
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,Adolescent ,Epidemiology ,mucosal ,Kaplan-Meier Estimate ,Nodular melanoma ,Acral lentiginous melanoma ,lcsh:RC254-282 ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Asian People ,Japan ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lentigo maligna melanoma ,Child ,Melanoma ,Survival analysis ,Original Research ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,acral ,Asian ,business.industry ,Mucosal melanoma ,Clinical Cancer Research ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Superficial spreading melanoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Child, Preschool ,Japanese ,Female ,Skin cancer ,business - Abstract
Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.
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- 2019
29. Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study
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Toshihiro Saito, Hiroshi Seki, Nobuaki Sato, Hiroshi Tanaka, Naohito Tanabe, Tatsuya Takenouchi, Tohru Minamino, Toshiki Tanigawa, Takaaki Chou, Kazuyuki Ozaki, Tsugumi Takayama, Akira Kikuchi, Yuji Okura, and Yasumasa Takii
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0301 basic medicine ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Cancer ,Hematology ,General Medicine ,Disease ,medicine.disease ,Comorbidity ,Cancer registry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Surgical oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Epidemiology ,medicine ,Surgery ,business ,education ,Disease burden - Abstract
The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center’s Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030–2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P
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- 2019
30. Real-world outcomes of Asian patients with advanced BRAF-mutant melanoma treated with first-line BRAF/MEK inhibitors, anti-PD-1 monotherapy, or combination of nivolumab plus ipilimumab: A multicenter retrospective study in Japan (B-CHECK-RWD study)
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Kenjiro Namikawa, Takamichi Ito, Shusuke Yoshikawa, Koji Yoshino, Yukiko Kiniwa, Tatsuya Takenouchi, Hiroshi Kato, Satoru Mizuhashi, Yosuke Yamamoto, Yasuhiro Fujisawa, Osamu Yamasaki, Yasuhiro Nakamura, Jun Asai, Takeo Maekawa, Shigeto Matsushita, Eiji Nakano, Kohei Oashi, Hisashi Uhara, Takuya Miyagawa, and Naoya Yamazaki
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Cancer Research ,Oncology - Abstract
e21553 Background: The systemic treatment for advanced BRAF-mutant melanoma includes BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (aPD1), and the combination of nivolumab plus ipilimumab (NIVO/IPI). Several studies have demonstrated favorable survival benefits for those treated with immunotherapy upfront. Most of these studies, however, were conducted among Caucasian-dominant cohorts; evidence for Asian patients is limited. Therefore, our objective was to assess the efficacy of first-line therapies for Asian patients in a real-world setting. Methods: We retrospectively collected the clinical data of Asian patients with advanced BRAF-mutant melanoma treated with first-line BRAF/MEKi, aPD1, or NIVO/IPI from 26 institutions in Japan. Clinical outcomes were determined by assessing the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) by first-line therapies. Kaplan‐Meier curves and log‐rank tests, as well as multivariable Cox proportional hazard models were used to estimate survival probabilities. Results: We identified 316 Asian patients treated with first-line BRAF/MEKi (n = 224), aPD1 (n = 59), or NIVO/IPI (n = 33) between 2016 and 2021. At baseline, the median age of the patients in each treatment arm was 63, 62, and 54, respectively (p = 0.053). The ORR in the first-line therapy was 69%, 29%, and 27%, respectively (p < 0.001). With a median follow-up of 18.9 months, the median PFS was 16.2, 5.6, and 6.4 months (p = 0.001); and the median OS was 36.9, 37.9 months, and not reached (p = 0.386), respectively. In a multivariable analysis, the predictive factors of short PFS were first-line therapy with aPD1 (HR, 2.44; 95%CI, 1.70-3.50, p < 0.001) or NIVO/IPI (1.73; 1.06–2.83, p = 0.029), BRAF V600K (p = 0.031), ECOG PS ≥2 (p = 0.011), elevated lactate dehydrogenase (LDH) levels (p = 0.001), and M1a/M1c/M1d stages (p = 0.036/ < 0.001/ < 0.001, respectively). Predictive factors of short OS were BRAF V600K (p = 0.042), ECOG PS ≥2 (p = 0.001), elevated LDH levels (p < 0.001), and M1c/M1d stages (both p < 0.001). The OS did not differ significantly by first-line therapies between BRAF/MEKi, aPD1 (1.52; 0.98–2.34, p = 0.061), and NIVO/IPI (0.63; 0.31–1.27, p = 0.194). Conclusions: Although upfront NIVO/IPI showed the longest OS numerically, its superiority over BRAF/MEKi in Asian patients seems to be modest compared with Caucasian patients. Because upfront BRAF/MEKi showed an OS that was comparable with that of aPD1, BRAF/MEKi remains an active first-line therapy option, especially for those who are not amenable to take the high risk of immune-related toxicities.
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- 2022
31. Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study
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Hironobu Minami, Suguru Asada, Hiroshi Uchi, Naoya Yamazaki, Hisashi Uhara, Masahiro Hatsumichi, Yoshio Kiyohara, Hiroshi Koga, Kenjiro Namikawa, Sumiko Takatsuka, Yoshinobu Namba, Naoko Wada, Shusuke Yoshikawa, and Tatsuya Takenouchi
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Gastrointestinal Diseases ,Phases of clinical research ,Kaplan-Meier Estimate ,Gastroenterology ,B7-H1 Antigen ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Japan ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Molecular Targeted Therapy ,Stage (cooking) ,Melanoma ,Aged, 80 and over ,Mucosal ,Drug Synergism ,Middle Aged ,Progression-Free Survival ,Neoplasm Proteins ,Nivolumab ,Oncology ,030220 oncology & carcinogenesis ,Female ,Immunotherapy ,Chemical and Drug Induced Liver Injury ,medicine.drug ,Adult ,medicine.medical_specialty ,Acral ,Ipilimumab ,Endocrine System Diseases ,03 medical and health sciences ,Internal medicine ,Humans ,Adverse effect ,Survival analysis ,Aged ,Asian ,business.industry ,medicine.disease ,Confidence interval ,030104 developmental biology ,Japanese ,business ,Follow-Up Studies - Abstract
Aim The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naive Japanese patients with advanced melanoma. Methods In this multicentre, single-arm study, treatment-naive Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. Results The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2–27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III–IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. Conclusions This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naive Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III–IV AEs were high but manageable with appropriate medical attention and treatment. Trial registration JapicCTI-152869.
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- 2018
32. Prospective observational study of the efficacy of nivolumab in Japanese patients with advanced melanoma (CREATIVE study)
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Naoya Yamazaki, Kazumi Kubota, Akira Takahashi, Takeharu Yamanaka, Kenjiro Namikawa, Yutaka Kawakami, Shigehisa Kitano, Tomonobu Fujita, Tatsuya Takenouchi, and Yasuhiro Nakamura
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0301 basic medicine ,Oncology ,Adult ,Male ,vitiligo ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,bias ,Adolescent ,Vitiligo ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Japan ,Internal medicine ,medicine ,melanoma ,Humans ,AcademicSubjects/MED00300 ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,post-marketing ,Adverse effect ,Lentigo maligna melanoma ,Aged ,Aged, 80 and over ,nivolumab ,Performance status ,business.industry ,Melanoma ,Mucosal melanoma ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Observational study ,Female ,Original Article ,Nivolumab ,business ,product surveillance - Abstract
Background Nivolumab, the anti-programmed cell death protein 1 antibody, has been approved for advanced melanoma, mainly based on evidence from Western countries. The profile of melanoma differs between Caucasian and Asian patients. This study was performed to obtain post-marketing data of nivolumab in Japanese patients with advanced melanoma. Methods This prospective, observational study involved patients with unresectable or metastatic melanoma treated with nivolumab at dosages of 2 mg/kg every 3 weeks or 3 mg/kg every 2 weeks. The primary endpoints were objective response rate and overall survival. The secondary endpoints were progression-free survival and the objective response rate according to immune-related Response Evaluation Criteria in Solid Tumours. Result Among 124 patients analysed, mucosal melanoma was the most common subtype, followed by acral lentiginous, nodular, superficial spreading and lentigo maligna melanoma. Response Evaluation Criteria in Solid Tumours evaluation showed an objective response rate of 17.7%. The median survival time was 15.93 months, and the 1-year overall survival rate was 66%. Outcomes were not significantly different among melanoma subtypes. Better overall survival and/or progression-free survival but not objective response rate were associated with performance status 0, lower levels of lactate dehydrogenase, C-reactive protein and neutrophil-to-lymphocyte ratio. Patients with immune-related adverse events showed a better objective response rate, 3-month landmark overall survival and progression-free survival than patients without immune-related adverse events. Conclusion The objective response rate and median survival time in Japanese patients treated with nivolumab were lower in daily practice than the >30% and >30 months, respectively, seen in global phase III trials. The occurrence of immune-related adverse events may be a predictor for survival and response to treatment with nivolumab., Efficacy of nivolumab was lower in post-marketing surveillance of Japanese patients with melanoma than in global trials. Immune-related adverse events were suggested to be efficacy predictors by 3-month landmark analysis.
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- 2020
33. Trends in the prognosis of metastatic melanoma in the era of targeted therapy and immunotherapy: A single-institution survey in Japan
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Tatsuya Takenouchi, Jin Sasaki, Sumiko Takatsuka, and Yu Matsui
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Oncology ,medicine.medical_specialty ,Metastatic melanoma ,medicine.medical_treatment ,Subgroup analysis ,Dermatology ,Targeted therapy ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,medicine ,Humans ,Single institution ,Melanoma ,Retrospective Studies ,business.industry ,Retrospective cohort study ,General Medicine ,Perioperative ,Immunotherapy ,medicine.disease ,Prognosis ,030220 oncology & carcinogenesis ,business - Abstract
Advances in anticancer therapy, including the development of targeted therapy and immunotherapy, have drastically changed treatment options for metastatic melanoma. However, to date, only a few studies have been published that directly compare overall survival (OS) before and after introduction of these new therapeutic options in Japan. We retrospectively surveyed patients with metastatic melanoma treated in our hospital between 1989 and 2019 to investigate the OS benefit of the new therapies. A total of 115 patients with metastatic melanoma (cutaneous origin, 92; mucosal, 14; uveal, two) were included in the study. Kaplan-Meier analysis showed that the patient group receiving targeted therapy/immunotherapy (TT/IT) (n = 47) had a median OS of 19.0 months, which was longer than that in patients receiving conventional chemotherapy (n = 42, 8.0 months) or no treatment (n = 26, 6.0 months) (P < 0.001). In the subgroup analysis performed for the TT/IT group, patients of younger age and with the BRAF mutation had significantly improved OS. As the number of treatment lines increased, the median OS tended to become longer. Our real-world data confirmed an improvement of median OS upon the introduction of the new therapies for metastatic melanoma. However, the long-term OS benefit was limited, possibly because of racial differences in some of the clinical characteristics. To improve the overall melanoma prognosis, the entire treatment strategy, including perioperative therapy needs strengthening.
- Published
- 2020
34. Final analysis of a phase II study of nivolumab in combination with ipilimumab for unresectable chemotherapy-naive advanced melanoma
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Hisashi Uhara, Naoko Wada, Naoya Yamazaki, Yoshio Kiyohara, Hiroshi Uchi, Hiroshi Koga, Shusuke Yoshikawa, Tatsuya Takenouchi, Sumiko Takatsuka, Masahiro Hatsumichi, Hironobu Minami, Kenjiro Namikawa, and Yoshinobu Namba
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,mucosal ,Phases of clinical research ,Ipilimumab ,Dermatology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,melanoma ,Humans ,ipilimumab ,Adverse effect ,nivolumab ,business.industry ,Melanoma ,General Medicine ,Original Articles ,medicine.disease ,Confidence interval ,Progression-Free Survival ,Discontinuation ,Radiation therapy ,030220 oncology & carcinogenesis ,Original Article ,Nivolumab ,business ,medicine.drug - Abstract
Nivolumab plus ipilimumab combination is currently one of the preferred regimens for advanced melanoma in recently updated clinical practice guidelines. However, the evidence on the efficacy of the combination for acral or mucosal subtypes remains less robust. This is the final analysis of a multicenter, open‐label, uncontrolled phase II study that investigated the long‐term efficacy and safety in treatment‐naive Japanese patients with advanced melanoma, including acral or mucosal subtypes, and subsequent therapy after discontinuation of the investigational agents. Patients received four doses of nivolumab (1 mg/kg i.v.) in combination with ipilimumab (3 mg/kg i.v.) at 3‐week intervals, followed by doses of nivolumab (3 mg/kg i.v.) at 2‐week intervals. The median follow‐up period was 20.8 months (range, 5.2–35.0). The centrally and locally assessed objective response rates were both 43.3% (13/30; 95% confidence interval [CI], 25.5–62.6). Median progression‐free survival was not reached (95% CI, 3.02–not reached), and median overall survival was also not reached (95% CI, 19.52–not reached). The 30‐month progression‐free survival and overall survival rates were 50.3% and 54.2%, respectively. No new safety concerns were detected. After discontinuation of the investigational agents, 83.3% of patients received some form of subsequent therapy including 43.3% of patients who received nivolumab monotherapy and 26.7% of patients who received radiotherapy. Of the four patients who discontinued the investigational agents because of immune‐related adverse events, two received subsequent therapy (nivolumab and ipilimumab, respectively) and the other two showed long‐term treatment‐free survival (659 and 590 days, respectively). Long‐term survival with nivolumab plus ipilimumab was observed in Japanese patients with melanoma including acral and mucosal subtypes, which is consistent with the CheckMate 067 study. Many patients continued to receive some form of treatment safely after stopping treatment with nivolumab plus ipilimumab.
- Published
- 2020
35. Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)
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Shintaro Saito, Y. Umeda, Yukiko Kiniwa, Yukiko Teramoto, Takashi Inozume, N. Yamazaki, Dai Ogata, Satoshi Fukushima, Noriki Fujimoto, Osamu Yamasaki, Tatsuya Takenouchi, Yasuo Nakai, A. Takahashi, Ryo Tanaka, Yasuhiro Nakamura, S. Yoshikawa, Takehiro Onuma, M. Otsuka, Kotaro Nagase, Yutaka Kuwatsuka, S. Matsushita, Natsuki Baba, Taisuke Matsuya, Motoo Nomura, Kenjiro Namikawa, Taiki Isei, Takahide Kaneko, Masazumi Onishi, Hiroshi Kato, Takeo Maekawa, and Atsushi Otsuka
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anti-PD-1 antibody ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,anti-CTLA-4 antibody ,Combination therapy ,chemical and pharmacologic phenomena ,Ipilimumab ,Pembrolizumab ,Gastroenterology ,Japan ,Internal medicine ,medicine ,Humans ,CTLA-4 Antigen ,mucosal melanoma ,ipilimumab ,Adverse effect ,Melanoma ,Aged ,Retrospective Studies ,Original Research ,nivolumab ,business.industry ,Hazard ratio ,Mucosal melanoma ,medicine.disease ,Confidence interval ,Oncology ,Immunotherapy ,pembrolizumab ,Nivolumab ,business ,medicine.drug - Abstract
Background Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. Patients and methods We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. Results Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). Conclusions First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events., Highlights • Anti-PD-1 plus anti-CTLA-4 antibody therapy (PD1 + CTLA4) is an option for patients with advanced mucosal melanoma (MCM). • Data on the efficacy of PD1 + CTLA4 compared with PD-1 monotherapy (PD1) for MCM, however, are limited. • We retrospectively analyzed data from 329 Japanese patients with advanced MCM treated with PD1 or PD1 + CTLA4. • No significant differences in objective response rate, progression-free survival, or overall survival were observed. • Immune-related adverse events resulting in treatment cessation were higher in the PD1 + CTLA4 group.
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- 2021
36. 1046P First-line anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy in Japanese mucosal melanoma: A retrospective, multicenter study (JMAC study)
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Taisuke Matsuya, Hiroshi Kato, Motoo Nomura, Tatsuya Takenouchi, Osamu Yamasaki, Kotaro Nagase, Yusuke Nakamura, Kenjiro Namikawa, Yasuo Nakai, Taiki Isei, Ryota Tanaka, S. Yoshikawa, Takashi Inozume, S. Saito, Yukiko Kiniwa, Takeo Maekawa, Atsushi Otsuka, Shigeto Matsushita, Satoshi Fukushima, and Natsuki Baba
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Oncology ,Multicenter study ,Combination therapy ,business.industry ,First line ,Anti pd 1 ,Cancer research ,Mucosal melanoma ,Medicine ,Hematology ,business ,medicine.disease ,Anti ctla 4 - Published
- 2021
37. Comparing the clinical efficacies of anti-PD-1 antibody monotherapy and anti-PD-1 and anti-CTLA-4 combination therapy as first-line immunotherapy in Japanese advanced acral melanoma: A retrospective, multicenter study (JAMP-neo study)
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Tatsuya Takenouchi, Takeo Maekawa, Ryo Tanaka, Taiki Isei, Takashi Inozume, Atsushi Otsuka, Shintaro Saito, Satoshi Fukushima, Noriki Fujimoto, Masazumi Onishi, Hiroshi Kato, Takahide Kaneko, Shusuke Yoshikawa, Yukiko Kiniwa, Shigeto Matsushita, Yasuo Nakai, Natsuki Baba, Yasuhiro Nakamura, Osamu Yamasaki, and Taisuke Matsuya
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Oncology ,Cancer Research ,medicine.medical_specialty ,Combination therapy ,biology ,business.industry ,First line ,medicine.medical_treatment ,Anti pd 1 ,Immunotherapy ,Anti ctla 4 ,Multicenter study ,Acral melanoma ,Internal medicine ,biology.protein ,Medicine ,Antibody ,business - Abstract
9542 Background: Anti-PD-1 antibody monotherapy (PD1) has been commonly used for patients with advanced acral melanoma (AM). However, recent studies have demonstrated the limited clinical efficacy of PD1 in AM compared to non-acral cutaneous melanoma, particularly in nail apparatus melanoma. Although advanced AM patients are strong candidates for first-line anti-PD-1 and anti-CTLA-4 combination therapy (PD1+CTLA4), data on the clinical efficacy of PD1+CTLA4 in AM are lacking. Thus, we aimed to compare the clinical efficacies of PD1+CTLA4 and PD1 in Japanese advanced AM patients. Methods: We retrospectively reviewed the clinical records of advanced AM patients treated with PD1+CTLA4 or PD1 as first-line immunotherapy at 23 Japanese institutions. Clinical response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Survival was estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 4.0. Results: A total of 192 patients (median age, 72 years) with advanced AM (palm and sole melanoma, 135; nail apparatus melanoma, 57) were included in the study. PD1+CTLA4 and PD1 were used as first-line immunotherapy in 39 and 153 patients, respectively. The baseline demographics and characteristics were similar between the PD1+CTLA4 and PD1 groups, except for age (median age 67.3 vs. 73.2; P = 0.005). The objective response rate (ORR) in PD1+CTLA4 was significantly higher than that of the PD1 group (38.5% vs. 16.3%; P = 0.047). The median progression-free survival (PFS) and overall survival (OS) in the PD1+CTLA4 group tended to be longer than those of the PD1 group, but the differences were not significant (median PFS 7.3 months vs. 4.5 months; P = 0.19, median OS 43.6 months vs. 18.2 months; P = 0.19). In the subgroup analysis of the palm and sole melanoma cohorts, no significant differences in ORR, PFS, and OS were observed between the PD1+CTLA4 and PD1 groups (ORR 31% vs. 20.8%; P = 0.67, median PFS 5.3 months vs. 5.9 months; P = 0.87, median OS not reached vs. 22.3 months; P = 0.66). Meanwhile, the nail apparatus melanoma cohort in the PD1+CTLA4 group exhibited significantly higher ORR, and longer PFS and OS than the PD1 group (ORR 60% vs 6.1%; P < 0.001; median PFS 19.6 months vs 3.8 months; P = 0.008, median OS 43.6 months vs 13.5 months; P = 0.049). Due to immune-related adverse events in all cohorts, the treatment cessation rate was higher in the PD1+CTLA4 group than the PD1 group (59% vs. 11.8%). Conclusions: PD1+CTLA4 was clinically more efficacious than PD 1 in advanced AM patients. Notably, advanced nail apparatus melanoma patients were strong candidates for first-line PD1+CTLA4.
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- 2021
38. Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study
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Naoya Yamazaki, Manabu Fujimoto, Hisashi Uhara, Hiroshi Uchi, Hironobu Ihn, Yoshio Kiyohara, Hironobu Minami, Masaki Otsuka, Tatsuya Takenouchi, and Jiro Uehara
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Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Phases of clinical research ,Antineoplastic Agents ,Vitiligo ,Immune checkpoint inhibitor ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Clinical Research ,Internal medicine ,Clinical endpoint ,melanoma ,Humans ,Medicine ,programmed death 1 (PD‐1) inhibitor ,Stage (cooking) ,Adverse effect ,Aged ,nivolumab ,business.industry ,Melanoma ,Antibodies, Monoclonal ,Original Articles ,General Medicine ,medicine.disease ,Confidence interval ,Survival Rate ,030104 developmental biology ,Japanese patients ,030220 oncology & carcinogenesis ,Immunology ,Disease Progression ,Original Article ,Female ,Neoplasm Recurrence, Local ,Nivolumab ,business ,programmed death 1 (PD-1) inhibitor - Abstract
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/ IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8–51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0–71.4). Treatment- related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.)
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- 2017
39. Randomized phase III trial of adjuvant therapy with locoregional interferon beta versus surgery alone in stage II/III cutaneous melanoma: Japan Clinical Oncology Group Study (JCOG1309, J-FERON)
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Tatsuya Takenouchi, Naoya Yamazaki, Hiroshi Uchi, Yoshio Kiyohara, Tetsuya Tsuchida, Tomonori Mizutani, Kenjiro Namikawa, Taro Shibata, Arata Tsutsumida, Shusuke Yoshikawa, Masutaka Furue, and Dai Ogata
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,Clinical Trial Note ,Medical Oncology ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Randomized controlled trial ,law ,melanoma ,medicine ,Adjuvant therapy ,Clinical endpoint ,Humans ,Radiology, Nuclear Medicine and imaging ,interferon beta ,Adverse effect ,business.industry ,Surrogate endpoint ,Patient Selection ,adjuvant therapy ,Interferon-beta ,General Medicine ,Combined Modality Therapy ,Surgery ,Clinical trial ,Treatment Outcome ,030104 developmental biology ,Oncology ,Dermatologic Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,randomized controlled trial ,Cutaneous melanoma ,business - Abstract
Randomized phase III trial (JCOG1309) has been started to confirm the superiority of adjuvant therapy with locoregional interferon beta over surgery alone in overall survival for patients with stage II/III cutaneous melanoma., The Dermatologic Oncology Group of Japan Clinical Oncology Group has started a randomized phase III trial to confirm the superiority of adjuvant therapy with locoregional interferon beta in overall survival over surgery alone for patients with pathological stage II/III cutaneous melanoma (JCOG1309). Patients in the interferon beta arm receive intra- or subcutaneous injections of interferon beta directly into the surgical site at a flat dose of 3 million units once per day. Treatment is repeated for 10 consecutive days every 8 weeks for a total of 3 courses during the induction phase, then 1-day injection every 4 weeks for 2.5 years. A total of 240 patients will be accrued from 17 Japanese institutions within 6.5 years. Primary endpoint is overall survival. Secondary endpoints are relapse-free survival, distant metastasis-free survival, pattern of recurrence, and adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000017494 [http://www.umin.ac.jp/ctr/index.htm].
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- 2017
40. Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma
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Tatsuya Takenouchi, Jiro Uehara, Hironobu Ihn, Taiki Isei, Naoya Yamazaki, Hiroshi Uchi, Hisashi Uhara, Hideaki Tahara, Yoshio Kiyohara, Hironobu Minami, Fujio Otsuka, Yasuhiro Fujisawa, Keiji Iwatsuki, and Hajime Iizuka
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0301 basic medicine ,Oncology ,programmed cell death‐1 ,Male ,Cancer Research ,medicine.medical_treatment ,Phases of clinical research ,programmed cell death-1 ,0302 clinical medicine ,Clinical endpoint ,Melanoma ,biology ,Antibodies, Monoclonal ,clinical trial ,General Medicine ,Interleukin-10 ,Survival Rate ,Cytokine ,Nivolumab ,030220 oncology & carcinogenesis ,Toxicity ,check-point inhibitor ,Disease Progression ,biomarker ,check‐point inhibitor ,Cytokines ,Original Article ,Female ,Antibody ,medicine.medical_specialty ,Antineoplastic Agents ,Disease-Free Survival ,03 medical and health sciences ,Interferon-gamma ,Clinical Research ,Internal medicine ,medicine ,Humans ,Adverse effect ,Aged ,business.industry ,Interleukin-6 ,Original Articles ,030104 developmental biology ,Tumor progression ,Immunology ,biology.protein ,Antibody therapy ,business ,Biomarkers - Abstract
Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.
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- 2017
41. 1110P Efficacy of salvage therapies after failure of anti-PD-1 monotherapy for advanced melanoma in an Asian population: A multi-institutional historical cohort study
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Takuya Miyagawa, S. Yoshikawa, Haruki Doi, Hisashi Uhara, Kenji Yokota, Naoya Yamazaki, Satoshi Fukushima, Yukiko Kiniwa, Takeru Funakoshi, Yukiko Teramoto, Yasuhiro Fujisawa, Takamichi Ito, Yasunobu Nakamura, Takeo Maekawa, Kenjiro Namikawa, Yoshitsugu Shibayama, Taiki Isei, Shigeto Matsushita, Koji Yoshino, and Tatsuya Takenouchi
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Anti pd 1 ,Asian population ,medicine ,Hematology ,business ,Historical Cohort ,Advanced melanoma - Published
- 2020
42. The Impending Epidemic of Cardiovascular Diseases in Patients With Cancer in Japan
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Tatsuya Takenouchi, Kazuyuki Ozaki, Yuji Okura, Tohru Minamino, Hiroshi Tanaka, and Nobuaki Sato
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,Antineoplastic Agents ,030204 cardiovascular system & hematology ,Multidisciplinary team ,Risk Assessment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Japan ,Risk Factors ,Neoplasms ,Epidemiology ,medicine ,Prevalence ,Humans ,In patient ,cardiovascular diseases ,Survivors ,Intensive care medicine ,education ,Epidemics ,Radiation Injuries ,Aged ,Aged, 80 and over ,education.field_of_study ,Radiotherapy ,business.industry ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Cancer treatment ,Clinical Practice ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Female ,Cardiology and Cardiovascular Medicine ,business ,Developed country - Abstract
Onco-cardiology, a new academic field, aims to improve the quality of life and prognosis of cancer patients and survivors with cardiovascular diseases (CVD). With the aging of the population, an epidemic of cancer with CVD is emerging in developed countries. Cancer and CVD share risk factors, pathophysiology, treatments, and preventive and rehabilitative measures. A multidisciplinary team-based approach is needed to support cancer treatment to maximize its effectiveness and minimize its cardiotoxic potential. Basic and clinical onco-cardiology are already being practiced harmoniously. However, systematization in academia and clinical practice and accumulation of evidence have just started. In this review, we present the epidemiology, common risk factors between cancer and CVD, future epidemic of CVD in patients with cancer, and the necessity for an onco-cardiological approach to managing the burden of CVD in cancer patients and survivors.
- Published
- 2019
43. Investigating the use of tie-over dressing after skin grafting
- Author
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Tatsuya Takenouchi, Akihiko Yuki, Hiroki Fujikawa, Riichiro Abe, and Sumiko Takatsuka
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Dermatology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Hematoma ,Graft take ,medicine ,Humans ,Aged ,Retrospective Studies ,Fixation (histology) ,Aged, 80 and over ,integumentary system ,business.industry ,Skin Transplantation ,General Medicine ,Middle Aged ,medicine.disease ,Bandages ,Wound infection ,Graft procedure ,Surgery ,body regions ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Seroma ,Operative time ,Skin grafting ,Female ,business ,human activities - Abstract
Tie-over bolster dressing after skin grafting can prolong operative time, and cause hematoma and seroma formation because of uneven pressure application. To describe the possibility of discontinuing the use of tie-over dressing, we carried out a retrospective comparative study of patients who underwent skin grafting at an institution between January 2009 and December 2014. We investigated and compared the take rate, healing period, wound infection rate and hematoma formation rate for the tie-over dressing group and the non-tie-over dressing group. Among 266 patients, 148 and 118 patients were included in the tie-over dressing group and non-tie-over dressing group, respectively. There were no significant differences between the take rate, healing period, wound infection rate and hematoma formation rate for the two groups. Multivariate analysis showed that the complete graft take rate was not significantly influenced by tie-over dressing, age, sex, graft site, graft procedure and skin graft diameter. Although the use of tie-over dressing might remain necessary on sites with a free margin, including the eyelids, lips or nostrils, because of the difficulty in using tape fixation, the present study showed that alternative dressing with polyurethane foam is also useful in most cases of skin grafting.
- Published
- 2017
44. Anti-PD-1 antibody therapy for epithelial skin malignancies
- Author
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Tatsuya Takenouchi, Kenjiro Namikawa, Atsushi Otsuka, Yuki Yamamoto, Keiji Tanese, Yasunori Sato, Masayuki Amagai, Takeru Funakoshi, Hiroshi Uchi, Ikuko Hirai, Naoya Yamazaki, Taku Fujimura, Mana Nishiguchi, Kenji Kabashima, Keitaro Fukuda, Takayuki Fusumae, Maki Ishii, Kenji Yokota, and Yoshio Nakamura
- Subjects
Adult ,Male ,Oncology ,anti-PD-1 antibody ,medicine.medical_specialty ,Skin Neoplasms ,medicine.drug_class ,Programmed Cell Death 1 Receptor ,Phases of clinical research ,malignant cutaneous epithelial tumors ,Monoclonal antibody ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Japan ,Study Protocol Clinical Trial ,Internal medicine ,medicine ,Carcinoma ,Humans ,Basal cell carcinoma ,030212 general & internal medicine ,Response Evaluation Criteria in Solid Tumors ,Neoplasm Staging ,nivolumab ,Response rate (survey) ,epithelial skin malignancies ,business.industry ,Epithelial Cells ,General Medicine ,medicine.disease ,Clinical trial ,Carcinoma, Basal Cell ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,Neoplasms, Adnexal and Skin Appendage ,Nivolumab ,business ,non-melanoma skin cancer ,Research Article - Abstract
Introduction: Malignant cutaneous epithelial tumors comprise various skin malignancies originating from the cutaneous epithelium, including cutaneous squamous cell carcinoma, basal cell carcinoma, and malignant cutaneous adnexal tumors. Treatment options are limited, as the rarity of these tumors, especially among Asians, renders well-controlled clinical trials extremely challenging to conduct. Thus, we designed a clinical trial to evaluate the efficacy and safety of the anti-programmed cell death-1 (PD-1) monoclonal antibody nivolumab in patients with metastatic cutaneous squamous cell carcinomas and other rare metastatic cutaneous epithelial tumors. Methods and analysis: This is an open-label, single-arm, multicenter, phase 2 clinical trial involving patients with metastatic malignant cutaneous epithelial tumors. Nivolumab (480 mg) will be administered intravenously every 4 weeks for a maximum of 26 doses. The primary outcome of the study will be the response rate based on response evaluation criteria in solid tumors, version 1.1. Assuming a null hypothesis of a response rate ≤5% and an alternative hypothesis of a 25% response rate, a minimum of 26 patients are required to achieve a 5% two-sided type I error and 80% power based on the exact binomial distribution. Finally, a target cohort size of 30 patients was determined as some patient dropout will be expected. Discussion: This is the first phase 2 clinical trial evaluating the efficacy and safety of the PD-1 inhibitor nivolumab in Asian patients with metastatic malignant cutaneous epithelial tumors. The findings of the study will contribute to the development of novel treatment approaches for patients with rare cutaneous malignancies, which remains an unmet clinical need. Trial registration: Registry number: jRCT 2031190048
- Published
- 2020
45. Response of nivolumab monotherapy in 124 Japanese patients with advanced melanoma: Interim analysis of prospective observational study (CREATIVE study)
- Author
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Shigehisa Kitano, Yutaka Kawakami, Takeharu Yamanaka, Yasuhiro Nakamura, Kazumi Kubota, A. Takahashi, Tatsuya Takenouchi, Kenjiro Namikawa, Tomonobu Fujita, and N. Yamazaki
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,Hematology ,Interim analysis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Acral melanoma ,Partial response ,Overall survival ,medicine ,In patient ,Nivolumab ,business ,Complete response ,Advanced melanoma - Abstract
Background Anti-PD-1 antibody nivolumab has been approved for advanced melanoma in Japan. Although there have been clinical trial reports on nivolumab treatment for advanced melanoma, real-world data on the efficacy of nivolumab in an Asian patient cohort is still lacking. The aim of this study is to obtain real-world data on the efficacy of nivolumab in Japanese patients with advanced melanoma. Methods This prospective observational study was performed on unresectable or metastatic melanoma patients who were treated with nivolumab. Primary endpoints were response rate (RR), and overall survival (OS). The secondary endpoints were progression-free survival (PFS) and the immune-related adverse events (irAEs) ratio. Results In total, 124 patients from 22 institutions in Japan were enrolled between Dec. 2015 and Dec. 2017. Mucosal melanoma (34%) was the most frequent subtype in this study, followed by acral lentiginous melanoma (20%), nodular melanoma (15%), superficial spreading melanoma (13%). We observed complete response (CR) in 2 (2%), partial response (PR) in 21 (17%), stable disease (SD) in 27 (22%), and progressive disease (PD) in 59 patients (47.6%) (objective RR: 19%). Use of nivolumab as first-line treatment showed a tendency toward higher response than when used as second-line treatment (objective RR, 23% vs 11%, P = 0.12). IrAEs comprised skin reactions and endocrine-related adverse effects. The median PFS in patients with skin reactions (or skin-related irAEs) was 8.61 months compared to 2.14 months without skin-related irAEs, and 8.99 months (p Conclusions The results of this interim analysis showed a lower RR than that reported in recent phase 2 trials conducted in Japan. The differences in the proportions of melanoma subtypes, with a higher proportion of mucosal and acral melanoma, and use of nivolumab as second-line treatment will probably lead to a lower RR to nivolumab in Japan. As the results of this study showed that the occurrence of irAEs had a significant impact on therapeutic efficiency, it is critical to take appropriate measures to manage the occurrence of irAEs. Legal entity responsible for the study The authors. Funding This study was sponsored by Public Health Research Foundation under the funding support from Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb K.K. Disclosure N. Yamazaki: Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: ONO Phamaceuticals; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Novartis Pharma K.K.; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: MSD K.K.; Honoraria (self), Honoraria (institution): Merck Serono Co., Ltd.; Honoraria (self): Takeda Pharmaceutical Co., Ltd. K. Namikawa: Honoraria (institution): Public Health Research Foundation; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp & Dohme. T. Takenouchi: Advisory / Consultancy: Ono Pharmaceutical Co., Ltd.; Advisory / Consultancy: MSD KK; Advisory / Consultancy: Chugai Pharmaceutical Co., LTD.; Advisory / Consultancy: Novartis Pharma KK. Y. Nakamura: Honoraria (self): ONO pharmaceuticals; Honoraria (self): MSD; Honoraria (self): Bristol Myers-Squibb; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Taisho Toyama Pharma; Honoraria (self): Maruho; Honoraria (self): Taiho Pharma. S. Kitano: Honoraria (self): AstraZeneca; Honoraria (self): Chugai; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Honoraria (self): Nippon Kayaku; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Meiji Seika Pharma; Honoraria (self): Taiho. T. Fujita: Honoraria (self): Public Health Research Foundation; Advisory / Consultancy: ONO PHARMACEUTICAL CO., LTD; Advisory / Consultancy: Bristol-Myers Squibb Company. T. Yamanaka: Honoraria (self), Honoraria (institution): Takeda; Honoraria (self), Honoraria (institution): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai. Y. Kawakami: Advisory / Consultancy: Public Health Research Foundation; Advisory / Consultancy: Ono Pharmaceutical Co., LTD; Advisory / Consultancy: Bristol-Myers Squibb Company. All other authors have declared no conflicts of interest.
- Published
- 2019
46. Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients
- Author
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Kazuyasu Fujii, Naoya Yamazaki, Yasuhiro Fujisawa, Tatsuya Takenouchi, Ryuhei Okuyama, Kaori Sakaizawa, Satoshi Fukushima, Jiro Uehara, Shigeto Matsushita, Aya Uchiyama, Dai Ogata, Hisashi Uhara, Takamichi Ito, Atsuko Ashida, Yoshitsugu Shibayama, and Naohito Hatta
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,Oncology ,Neuroblastoma RAS viral oncogene homolog ,medicine.medical_specialty ,Pathology ,Skin Neoplasms ,Dermatology ,Gene mutation ,medicine.disease_cause ,Biochemistry ,GTP Phosphohydrolases ,law.invention ,symbols.namesake ,Asian People ,Japan ,law ,Internal medicine ,medicine ,Humans ,Melanoma ,Molecular Biology ,Pathological ,Polymerase chain reaction ,Aged ,Skin ,Sanger sequencing ,Mutation ,business.industry ,Membrane Proteins ,Middle Aged ,medicine.disease ,Proto-Oncogene Proteins c-kit ,medicine.anatomical_structure ,Scalp ,symbols ,Female ,business - Abstract
Background The importance of the genetic background of melanoma cells to the individual susceptibility to treatment has become apparent. In Caucasians, BRAF mutations are frequently detected in lesions on the skin of younger patients compared to NRAS and KIT mutations. However, clinical and pathological characteristics associated with BRAF , NRAS and KIT mutations have not been fully evaluated in East Asians. Objective To clarify clinical and pathological characteristics associated with BRAF , NRAS and KIT mutations in Japanese melanoma patients. Methods Clinical data were retrospectively collected from 11 hospitals in Japan. BRAF , NRAS and KIT mutations were evaluated with polymerase chain reaction and Sanger sequencing. The relationships between these gene mutations and pathological and clinical findings were analyzed. Results The number of cases examined was 171 (primary: 135, metastases: 11, paired: 25), and all were Japanese patients. The detection rates of BRAF , NRAS and KIT mutations were 30.4%, 12.3% and 12.9%, respectively. Compared with the wild type, the presence of BRAF mutations was significantly associated with younger age (median, 50.0 years vs. 70.0 years, p BRAF mutation was frequently detected in the lesions of the scalp (80%; 4/5), trunk (72.0%; 18/25), extremities (56.7%; 17/30) and neck (44.4%; 4/9), and the least prevalent were the face (22.2%; 2/9), nail (12.5%; 3/24), palm or sole (8.9%; 4/45) and mucosa (0%). NRAS mutations were prevalent in the face (33.3%) and palm or sole (20.0%), and the median age of these patients was 70.5 years. A KIT mutation was observed in the nail apparatus (25%), palm or sole (15.6%) and mucosa (18.2%). The median age of the patients with a KIT mutation was 63.0 years. Heterogeneity of mutations between primary and metastatic lesions was detected in six of 25 cases (24%). Solar elastosis was identified in 12 of 71 cases (15.3%), among which four cases harbored BRAF V600E (2 cases), BRAF V600K , NRAS Q61K or NRAS Q61L , respectively. Conclusion Some clinical characteristics associated with BRAF , NRAS and KIT mutations were observed in Japanese patients, and we observed both similarities to and differences from those of Caucasians. Our findings could provide useful information in efforts to clarify the tumor genesis of malignant melanomas.
- Published
- 2015
47. A case of pure red cell aplasia during nivolumab therapy for cardiac metastatic melanoma
- Author
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Takuro Ishiguro, Sumiko Takatsuka, Tatsuya Takenouchi, and Akihiko Yuki
- Subjects
Cancer Research ,Metastatic melanoma ,Heart Diseases ,Pure red cell aplasia ,Antineoplastic Agents ,Dermatology ,Red-Cell Aplasia, Pure ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Neoplasm Metastasis ,Adverse effect ,Melanoma ,Pneumonitis ,Aged ,Hepatitis ,biology ,business.industry ,Antibodies, Monoclonal ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Rash ,Nivolumab ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,biology.protein ,Female ,Antibody ,medicine.symptom ,business ,030215 immunology - Abstract
Nivolumab is an antibody against programmed cell death 1 and functions as an immune checkpoint inhibitor for various malignancies, including unresectable melanomas. Nivolumab causes several immune-related adverse events, which typically include skin rash, pneumonitis, thyroid dysfunction, hepatitis, and colitis; in rare cases, anemia may be present. There are several reports of autoimmune hemolytic anemia that has developed in response to nivolumab; however, there are few reports of pure red cell aplasia (PRCA). We describe a patient who developed PRCA during nivolumab administration. A 70-year-old Japanese woman received nivolumab for cardiac metastasis from malignant melanoma from an unknown site. Twenty-one months after nivolumab administration (31 courses), treatment was discontinued because she developed severe anemia. Blood test results indicated normocytic, normochromic anemia, and reticulocytopenia, but all other components were normal. Bone marrow aspiration showed increased megakaryocytes and decreased erythroblasts; these findings were consistent with PRCA. Anemia improved without recurrence after treatment with corticosteroids and blood transfusions. The steroid dosage was reduced gradually, and to date, the patient has not experienced recurrence of anemia. The tumor decreased in size and the patient has shown a continued response to treatment with decrease in disease for 3 years. Although it is unclear how nivolumab causes PRCA, hematological toxicities have been reported in patients treated with immunotherapy drugs. PRCA might be an unrecognized immune-mediated adverse event that did not manifest during the clinical trial phase.
- Published
- 2017
48. Final results from phase II of combination with canerpaturev (formerly HF10), an oncolytic viral immunotherapy, and ipilimumab in unresectable or metastatic melanoma in second-or later line treatment
- Author
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Naoya Yamazaki, Satoshi Fukushima, Hiroshi Uchi, Kenji Yokota, Hiroshi Saruta, Hironobu Ihn, Hisashi Uhara, Taiki Isei, A. Takahashi, Takashi Inozume, Yoshio Kiyohara, Daisuke Watanabe, Tatsuya Takenouchi, Maki Tanaka, and Yasuhiro Fujisawa
- Subjects
0301 basic medicine ,Kyowa hakko ,Metastatic melanoma ,business.industry ,Best Overall Response ,Treatment options ,Tumor cells ,Hematology ,Disease control ,Management ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Pharmacy (field) ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,business ,Response criteria - Abstract
Background Canerpaturev (C–REV) is an oncolytic, spontaneous mutant of HSV-1, and is one of immunotherapies that can not only kill tumor cells but also modulate immune responses. We report the efficacy of Phase II multicenter trial of combination therapy using C-REV and ipilimumab (ipi) in melanoma patients (pts) who were refractory or intolerant to prior therapies. Methods Key entry criteria: age ≥ 20 yrs, ECOG PS 0-2, AJCC 7th Stage IIIB-IV unresectable melanoma, who received prior therapies and had measurable non-visceral lesion(s) suitable for C-REV injections. C-REV was injected into each tumor (1 x 107 TCID50/mL/dose, up to 5 mL); 4 injections q1wk; then up to 15 injections q3wks. Ipi (3 mg/kg) was administered 4 times, q3wks. Primary endpoint was Best Overall Response Rate (BORR) by immune-related response criteria (irRC). Results 28 pts were enrolled. Disease stage: 7.1% IIIB, 28.6% IIIC and 64.3% IV, and disease type: 39.3% acral lentiginous and 21.4% mucosal melanoma. Anti-PD-1 antibody was previously used in 89.3%. Severe adverse events (AEs, ≥G3) related to the study treatment was 35.7 %. Of 27 efficacy evaluable pts, BORR and disease control rate by irRC 11.1% and 55.6%, respectively. Pts with irPR and durable irSD longer than 24 wks were confirmed in 22.2 % (6 pts) and had no deaths (follow-up period: 298 - 446 days). The median OS was 318.0 days (95% C.I. 211.00 – not reached). Conclusions In melanoma, various immunotherapies and molecular targeted drugs have been approved for treatment options, but there are still unmet medical needs in particular in pts who failed in the 1st line therapy. In this trial, C-REV did not show the exacerbation in ipi toxicity and patients with irPR and durable irSD contributed to prolonging OS. Thus, C-REV plus ipi has potential to become a new treatment option for melanoma in ≥ 2nd-line setting. Clinical trial identification NCT03153085. Legal entity responsible for the study Takara Bio Inc. Funding Takara Bio Inc. Disclosure K. Yokota: Research grant / Funding (institution): Takara Bio Inc. T. Isei: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ono Pharmaceutical Co., Ltd.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis Pharma K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD K.K.; Honoraria (self): Mochida Pharmaceutical Co., Ltd.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self), Travel / Accommodation / Expenses: Kaken Pharmaceutical Co.,Ltd.; Honoraria (self): Daiichi Sankyo Company, Limited.; Honoraria (self), Travel / Accommodation / Expenses: Maruho Co.,Ltd. ; Honoraria (self), Travel / Accommodation / Expenses: Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): POLA-Pharma; Advisory / Consultancy: Merck Biopharma Co., Ltd; Research grant / Funding (institution): Takara Bio Inc.; Research grant / Funding (institution): Array BioPharma, Inc.; Research grant / Funding (institution): Amgen Inc. H. Uhara: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono Pharmaceutical Co., LTD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD K.K.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis Pharma K.K.; Honoraria (self), Research grant / Funding (institution): Maruho Co.,Ltd. ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb K.K.; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): POLA-Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa Hakko Kirin Co., Ltd.; Speaker Bureau / Expert testimony: Janssen Pharmaceutical K.K.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Mitsubishi Tanabe Pharma Corporation; Research grant / Funding (institution): Taiho Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Eisai Co., Ltd. ; Research grant / Funding (institution): AbbVie GK.; Research grant / Funding (institution): Maruho Co.,Ltd. ; Research grant / Funding (institution): Daiichi Sankyo Company, Limited. ; Research grant / Funding (institution): Tsumura & Co.; Research grant / Funding (institution): Mochida Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Nippon Kayaku Co.,Ltd.; Research grant / Funding (institution): Torii Pharmaceutical Co.,Ltd; Research grant / Funding (institution): Kaken Pharmaceutical Co.,Ltd. Y. Fujisawa: Advisory / Consultancy: Eli Lilly Japan K.K. ; Advisory / Consultancy: Novartis Pharma K.K.; Research grant / Funding (institution): Ono Pharmaceutical Co., LTD; Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Research grant / Funding (institution): Eisai Co., Ltd. ; Research grant / Funding (institution): Takara Bio Inc. T. Takenouchi: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: MSD K.K.; Speaker Bureau / Expert testimony: Novartis Pharma K.K.; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Bristol-Myers Squibb K.K.; Research grant / Funding (institution): Takara Bio Inc. Y. Kiyohara: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Toray Industries, Inc.; Honoraria (self), Research grant / Funding (institution): Merck Biopharma Co., Ltd; Honoraria (self): Boehringer Ingelheim Japan, Inc.; Research grant / Funding (institution): Takara Bio Inc.; Honoraria (self), Research grant / Funding (institution): Amgen Inc. H. Uchi: Research grant / Funding (institution): Takara Bio Inc. H. Saruta: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Kyowa Hakko Kirin Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Minophagen Pharmaceutical Co., LTD.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Takara Bio Inc. H. Ihn: Research grant / Funding (institution): Takara Bio Inc. T. Inozume: Research grant / Funding (institution): Takara Bio Inc. D. Watanabe: Advisory / Consultancy: Japan vaccine; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Maruho Co.,Ltd. ; Research grant / Funding (institution): Sanofi K.K.; Research grant / Funding (institution): Nippon Zoki Pharmaceutical Co., Ltd. ; Research grant / Funding (institution): Daiichi Sankyo Company, Limited.; Research grant / Funding (institution): Takara Bio Inc. A. Takahashi: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self), Research grant / Funding (institution): Novartis Pharma K.K.; Research grant / Funding (institution): Takara Bio Inc. S. Fukushima: Research grant / Funding (institution): Takara Bio Inc. M. Tanaka: Full / Part-time employment: Takara Bio Inc. N. Yamazaki: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma K.K.; Research grant / Funding (institution): Takara Bio Inc.
- Published
- 2019
49. Primary analysis results of randomized controlled trial evaluating reactive topical corticosteroid strategies for the facial acneiform rash by EGFR inhibitors (EGFRIs) in patients (pts) with RAS wild-type (wt) metastatic colorectal cancer (mCRC): FAEISS study
- Author
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Taro Shibata, Akiko Hasegawa, Masahiro Takahashi, Katsuko Kikuchi, S. Takatsuka, Atsuo Takashima, Toshiki Masuishi, Tatsuya Takenouchi, K. Hino, Kentaro Yamazaki, Tetsuya Hamaguchi, S. Yoshikawa, Tomohiro Nishina, Narikazu Boku, Yoshio Kiyohara, Kazuki Nozawa, Haruhiko Fukuda, Hirokazu Shoji, Naoya Yamazaki, and Hiroko Bando
- Subjects
medicine.medical_specialty ,business.industry ,Significant difference ,Acneiform rash ,Hematology ,law.invention ,Clinical trial ,Oncology ,Topical corticosteroid ,Randomized controlled trial ,law ,Internal medicine ,medicine ,In patient ,business ,Standard therapy ,EGFR inhibitors - Abstract
Background The management strategies regarding the strength of reactive topical corticosteroids have not been well evaluated in clinical trials. This FAEISS study is designed to confirm the superior efficacy of reactive topical corticosteroid strategies with serially ranking-DOWN from very strong levels compared with those with serially ranking-UP from weak levels for facial acneiform rash induced by EGFRI. Methods Pts with RAS wt mCRC were enrolled in the first registration. All pts received pre-emptive therapy with oral minocycline 100 or 200 mg/day and heparinoid moisturizer from the initiation of EGFRIs. Enrolled pts who developed facial acneiform rash within 8 weeks were randomized either to ranking-UP group (UP group) or ranking-DOWN group (DOWN group) (second registration) using minimization method for balancing institution, type of EGFRIs, and sex. Primary endpoint was incidence of Grade2 (moderate) or higher facial acneiform rash during 8 weeks after randomization. Results 172 RAS wt mCRC pts, of whom 22 pts and 84 pts received cetuximab and panitumumab, respectively, were enrolled and 106 pts were randomized. There was no significant difference in the incidence of Grade 2 ≧ facial acneiform rash between UP group (18 times) and DOWN group (20 times) (stratified Wilcoxon’s rank sum test, one-sided: p = 0.86221). As for secondary end points, proportion of Grade3 or higher facial acneiform rash was 13.2% for UP group and 11.3% for DOWN group, showing no significant difference between the groups (Fisher’s exact test: p = 1.0000). There was no problem of safety concern in both groups. Conclusions Topical corticosteroids ranking UP from weak levels was confirmed to be standard therapy for the management of facial acneiform rash in pts with RAS wt mCRC. It would follow that minocycline and heparinoid moisturizer have a prophylactic efficacy while topical corticosteroids have a therapeutic efficacy for facial acneiform rash. Clinical trial identification UMIN000024113. Legal entity responsible for the study FAEISS Study Group. Funding AMED. Disclosure N. Yamazaki: Honoraria (self), Research grant / Funding (institution): Takarabio; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis. K. Kikuchi: Research grant / Funding (institution): POLA; Research grant / Funding (institution): Maruho. H. Fukuda: Honoraria (self): Taiho/chugai; Research grant / Funding (self): National Cancer Center. T. Hamaguchi: Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self): Takeda; Honoraria (self): Bayer. N. Boku: Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb. T. Takenouchi: Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Novartis . T. Nishina: Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Merck Serono. S. Yoshikawa: Honoraria (self): Ono; Honoraria (self): Novertis; Honoraria (self): Bristol-Myers Squibb. K. Yamazaki: Honoraria (self): Chugai; Honoraria (self): Daiichi Sankyo. M. Takahashi: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono; Speaker Bureau / Expert testimony: Daiichi Sankyo. T. Masuishi: Honoraria (self): Taiho; Honoraria (self): Merck Serono; Honoraria (self): Yakult Honsha. Y. Kiyohara: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ono; Honoraria (self), Research grant / Funding (institution): BMS. All other authors have declared no conflicts of interest.
- Published
- 2019
50. Real-world efficacy of anti-PD-1 antibodies in advanced acral melanoma patients: A retrospective, multicenter study (JAMP study)
- Author
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Atsushi Otsuka, Naoya Yamazaki, Haruki Doi, Hisashi Uhara, Yukiko Teramoto, Dai Ogata, Hiroshi Uchi, Katsunobu Goto, Takeru Funakoshi, Koji Yoshino, Shigeto Matsushita, Kenjiro Namikawa, Yoshiyuki Nakamura, Satoshi Fukushima, Yasuhiro Nakamura, Naohito Hatta, Tatsuya Takenouchi, Toru Kawai, Shusuke Yoshikawa, and Yukiko Kiniwa
- Subjects
Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,Anti pd 1 ,Dermatology ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Multicenter study ,030220 oncology & carcinogenesis ,Acral melanoma ,Cutaneous melanoma ,biology.protein ,Medicine ,Antibody ,business ,030215 immunology ,Advanced melanoma - Abstract
9529 Background: Anti-PD-1 antibodies are used worldwide for patients (pts) with advanced melanoma. Clinical trials have demonstrated its efficacy and safety for nonacral cutaneous melanoma (NACM) in controlled settings. Since acral melanoma (AM) is epidemiologically and molecularly distinct from NACM, data on the real-world efficacy of anti-PD1 antibodies in advanced AM is still lacking. Thus, we aim to analyze the real-world efficacy and safety of anti-PD-1 antibodies in advanced AM. Methods: We retrospectively reviewed clinical records of advanced AM treated in any line with an anti-PD1 antibody at 21 Japanese institutions. Clinical response was assessed by (Response Evaluation Criteria in Solid Tumors) RECIST criteria. Survival was estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 4.0. Results: A total of 193 pts (median age, 71 years) with advanced AM (subungual, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 pts (74.1%). Nivolumab was used in 168 pts and pembrolizumab in 25 pts. Base-line lactate dehydrogenase (LDH) was within normal level in 102 pts (52.8%). The objective response rate (ORR) of all pts was 16.5% (complete response 3.1%, partial response 13.5%), and median overall survival (OS) was 18.1 months. Normal LDH level was significantly associated with better prognosis than abnormal level (median OS 24.9 vs 10.7 months; P < 0.001). Although baseline demographics and characteristics were almost similar between subungual group and palm and sole group, ORR was significantly lower in the subungual group than in palm and sole group (6/70 pts [8.6%] vs 26/123 pts [21.1%]; P = 0.026); median OS was significantly poorer as well (12.8 vs 22.3 months; P = 0.031). Immune-related adverse events of grades 3 to 5 occurred in 27 pts (14.0%). One patient (0.5%) died of grade 5 myasthenia gravis. Conclusions: Real-world efficacy of anti-PD-1 antibodies in AM pts is limited. Notably, pts with subungual melanoma showed poorer response and survival, making them strong candidates for further research of efficacy of anti-CTLA-4 and anti-PD-1 combination therapy.
- Published
- 2019
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