34 results on '"Kitazono S"'
Search Results
2. Ore minerals of the Doyashiki Kuroko deposits, Hokuroku basin, Japan
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Kitazono, S., primary and Ueno, H., additional
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- 2022
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3. EP02.01-006 Advances in the Treatment of Postoperative Recurrence of Non-Small Cell Lung Cancer and Their Real-World Impact on Survival
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Hashimoto, K., primary, Ariyasu, R., additional, Ichinose, J., additional, Matsuura, Y., additional, Nakao, M., additional, Amino, Y., additional, Uchibori, K., additional, Kitazono, S., additional, Yanagitani, N., additional, Okumura, S., additional, Nishio, M., additional, and Mun, M., additional
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- 2022
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4. P47.06 TROPION-Lung04: Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab and Platinum-Based Chemotherapy in Advanced NSCLC
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Borghaei, H., primary, Gutierrez, M., additional, Waqar, S., additional, Kitazono, S., additional, Yin, J., additional, Xie, J., additional, Guevara, F., additional, and Papadopoulos, K., additional
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- 2021
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5. MA03.02 TROPION-PanTumor01: Updated Results From the NSCLC Cohort of the Phase 1 Study of Datopotamab Deruxtecan in Solid Tumors
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Garon, E., primary, Johnson, M., additional, Lisberg, A., additional, Spira, A., additional, Yamamoto, N., additional, Heist, R., additional, Sands, J., additional, Yoh, K., additional, Meric-Bernstam, F., additional, Kitazono, S., additional, Greenberg, J., additional, Kobayashi, F., additional, Guevara, F., additional, Kawasaki, Y., additional, and Shimizu, T., additional
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- 2021
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6. LBA49 Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): Preliminary results from the phase I TROPION-PanTumor01 study
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Garon, E.B., primary, Johnson, M.L., additional, Lisberg, A.E., additional, Spira, A., additional, Yamamoto, N., additional, Heist, R.S., additional, Sands, J.M., additional, Yoh, K., additional, Meric-Bernstam, F., additional, Kitazono, S., additional, Greenberg, J., additional, Kobayashi, F., additional, Kawasaki, Y., additional, Jukofsky, L., additional, Nakamura, K., additional, and Shimizu, T., additional
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- 2021
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7. 1249P Pharmacokinetic and dose finding study of osimertinib in patients with impaired renal function and low body weight
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Hase, T., primary, Fujiwara, Y., additional, Makihara, R.A., additional, Hashimoto, N., additional, Tsubata, Y., additional, Okuno, T., additional, Naito, T., additional, Takahashi, T., additional, Kobayashi, H., additional, Shinno, Y., additional, Ikeda, T., additional, Goto, K., additional, Hosomi, Y., additional, Watanabe, K., additional, Kitazono, S., additional, Sakiyama, N., additional, Makino, Y., additional, and Yamamoto, N., additional
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- 2021
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8. LBA12 Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01
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Ahn, M-J., Lisberg, A., Paz-Ares, L., Cornelissen, R., Girard, N., Pons-Tostivint, E., Vicente Baz, D., Sugawara, S., Cobo Dols, M., Pérol, M., Mascaux, C., Poddubskaya, E., Kitazono, S., Hayashi, H., Sands, J., Hall, R., Zhang, Y., Zebger-Gong, H., Uema, D., and Okamoto, I.
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- 2023
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9. LBA5 Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study
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Girard, N., Park, K., Tang, K., Cho, B.C., Paz-Ares, L., Cheng, S., Kitazono, S., Thiagarajan, M., Goldman, J.W., Sabari, J.K., Sanborn, R.E., Mansfield, A.S., Hung, J-Y., Popat, S., Dias, J., Bhattacharya, A., Agrawal, T., Shreeve, M., Knoblauch, R.E., and Zhou, C.
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- 2023
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10. 1314MO TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs)
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Paz-Ares, L., Ahn, M-J., Lisberg, A.E., Kitazono, S., Cho, B.C., Blumenschein, G., Shum, E., Pons-Tostivint, E., Goto, Y., Yoh, K., Heist, R., Baas, P., Planchard, D., Pérol, M., Felip, E., Su, W-C., Zebger-Gong, H., Lan, L., Liu, C., and Sands, J.
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- 2023
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11. 518MO TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs).
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Kitazono, S., Paz-Ares, L., Ahn, M-J., Lisberg, A.E., Cho, B.C., Blumenschein, G., Shum, E., Pons-Tostivint, E., Goto, Y., Yoh, K., Heist, R., Baas, P., Planchard, D., Pérol, M., Felip, E., Su, W-C., Zebger-Gong, H., Lan, L., Liu, C., and Sands, J.
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NON-small-cell lung carcinoma - Published
- 2023
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12. Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase 3 study TROPION-Lung01.
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Atmaca, A, Ahn, M, Lisberg, A, Paz-Ares, L, Cornelissen, R, Girard, N, Pons-Tostivint, E, Baz, D, Sugawara, S, Cobo, M, Pérol, M, Mascaux, C, Poddubskaya, E, Kitazono, S, Hayashi, H, Sands, J, Hall, R, Zhang, Y, Zebger-Gong, H, and Okamoto, I
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- 2024
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13. OA05.06 Datopotamab Deruxtecan (Dato-DXd) + Durvalumab ± Carboplatin in Advanced/mNSCLC: Initial Results from Phase 1b TROPION-Lung04.
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Papadopoulos, K.P., Bruno, D., Kitazono, S., Murakami, S., Gutierrez, M., Wakuda, K., Spira, A., Cuppens, K., Lovick, S., Hepner, A., Mak, G., and Waqar, S.N.
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- 2023
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14. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions.
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Zhou, C., Tang, K.-J., Cho, B. C., Liu, B., Paz-Ares, L., Cheng, S., Kitazono, S., Thiagarajan, M., Goldman, J. W., Sabari, J. K., Sanborn, R. E., Mansfield, A. S., Hung, J.-Y., Boyer, M., Popat, S., Dias, J. Mourio, Felip, E., Majem, M., Gumus, M., and Kim, S.
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EPIDERMAL growth factor receptors , *POISONS , *NON-small-cell lung carcinoma , *CANCER chemotherapy - Abstract
BACKGROUND Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed. METHODS In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivanta- mab-chemotherapy) or chernotherapy alone. The prirnary outcome was progres- sion-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy. METHODS In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivanta- mab-chemotherapy) or chernotherapy alone. The prirnary outcome was progres- sion-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy. RESULTS A total of 308 patients underwent randomization (153 to receive amivantamabchemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3°6 in the chemotherapy group; a complete or partial response at data cutoffwas reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P=0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFRrrelated toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions. CONCLUSIONS The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.) [ABSTRACT FROM AUTHOR]
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- 2023
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15. 552P TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in Asian patients (pts) with previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs).
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Ahn, M-J., Cho, B.C., Goto, Y., Yoh, K., Su, W-C., Shimizu, J., Lee, J-S., Oizumi, S., Yang, J.C-H., Hayashi, H., Zebger-Gong, H., Sugiura, K., Lan, L., Liu, C., and Kitazono, S.
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NON-small-cell lung carcinoma , *ASIANS - Published
- 2023
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16. 513MO Amivantamab plus chemotherapy vs chemotherapy as a first-line treatment among Asian patients with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): PAPILLON subgroup analysis.
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Zhou, C., Tang, K., Liu, B., Kim, S-W., Kitazono, S., Ono, A., Thiagarajan, M., Hung, J-Y., Boyer, M., Xie, J., Bhattacharya, A., Baig, M., Agrawal, T., Knoblauch, R.E., and Cho, B.C.
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NON-small-cell lung carcinoma , *ASIANS , *EPIDERMAL growth factor receptors , *SUBGROUP analysis (Experimental design) , *CANCER chemotherapy - Published
- 2023
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17. 509MO Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01.
- Author
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Ahn, M-J., Lisberg, A.E., Paz-Ares, L., Cornelissen, R., Girard, N., Pons-Tostivint, E., Vicente Baz, D., Sugawara, S., Cobo Dols, M., Pérol, M., Mascaux, C., Poddubskaya, E., Kitazono, S., Hayashi, H., Sands, J., Hall, R., Zhang, Y., Zebger-Gong, H., Uema, D., and Okamoto, I.
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NON-small-cell lung carcinoma , *DOCETAXEL , *METASTASIS - Published
- 2023
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18. Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study.
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Ahn MJ, Tanaka K, Paz-Ares L, Cornelissen R, Girard N, Pons-Tostivint E, Vicente Baz D, Sugawara S, Cobo M, Pérol M, Mascaux C, Poddubskaya E, Kitazono S, Hayashi H, Hong MH, Felip E, Hall R, Juan-Vidal O, Brungs D, Lu S, Garassino M, Chargualaf M, Zhang Y, Howarth P, Uema D, Lisberg A, and Sands J
- Abstract
Purpose: The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non-small cell lung cancer (NSCLC)., Methods: Patients received Dato-DXd 6 mg/kg or docetaxel 75 mg/m
2 once every 3 weeks. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Objective response rate, duration of response, and safety were secondary end points., Results: In total, 299 and 305 patients were randomly assigned to receive Dato-DXd or docetaxel, respectively. The median PFS was 4.4 months (95% CI, 4.2 to 5.6) with Dato-DXd and 3.7 months (95% CI, 2.9 to 4.2) with docetaxel (hazard ratio [HR], 0.75 [95% CI, 0.62 to 0.91]; P = .004). The median OS was 12.9 months (95% CI, 11.0 to 13.9) and 11.8 months (95% CI, 10.1 to 12.8), respectively (HR, 0.94 [95% CI, 0.78 to 1.14]; P = .530). In the prespecified nonsquamous histology subgroup, the median PFS was 5.5 versus 3.6 months (HR, 0.63 [95% CI, 0.51 to 0.79]) and the median OS was 14.6 versus 12.3 months (HR, 0.84 [95% CI, 0.68 to 1.05]). In the squamous histology subgroup, the median PFS was 2.8 versus 3.9 months (HR, 1.41 [95% CI, 0.95 to 2.08]) and the median OS was 7.6 versus 9.4 months (HR, 1.32 [95% CI, 0.91 to 1.92]). Grade ≥3 treatment-related adverse events occurred in 25.6% and 42.1% of patients, and any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8.8% and 4.1% of patients, in the Dato-DXd and docetaxel groups, respectively., Conclusion: Dato-DXd significantly improved PFS versus docetaxel in patients with advanced/metastatic NSCLC, driven by patients with nonsquamous histology. OS showed a numerical benefit but did not reach statistical significance. No unexpected safety signals were observed.- Published
- 2024
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19. High-cost treatments for advanced lung cancer in Japan (Lung Cancer Study Group of the Japan Clinical Oncology Group).
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Watanabe K, Sasaki K, Machida R, Shimizu J, Yamane Y, Tamiya M, Saito S, Takada Y, Yoh K, Yoshioka H, Murakami H, Kitazono S, Goto Y, Horinouchi H, and Ohe Y
- Abstract
Background: The treatment of lung cancer has made dramatic progress in the past decade, but due to the high cost of drugs, the total pharmaceutical cost has been rising explosively. There are currently no data available in Japan on which regimens are used, to what extent they are used, and what their total cost is., Methods: Sixty Japanese centers belonging to the Lung Cancer Study Group of the Japan Clinical Oncology Group were surveyed for information about the first-line treatment for advanced lung cancer in practice from July 2021 to June 2022. Three types of cancer were included: driver gene mutation-negative NSCLC, EGFR mutation-positive NSCLC, and extensive-stage small cell lung cancer (ES-SCLC)., Results: Recent treatment costs for ICIs or ICI plus chemotherapy were about 20-55 times higher than those for conventional chemotherapy. Of the 3738 patients with driver gene aberration-negative NSCLC, 2573 (68.8%) received treatments with monthly cost of 500 000 Japanese yen (JPY) or more; 2555 (68.4%) received ICI therapy. Of the 1486 patients with EGFR mutation-positive NSCLC, 1290 (86.8%) received treatments with a monthly cost of 500 000 JPY or more; 1207 (81.2%) received osimertinib. ICI treatments with a monthly cost of 500 000 JPY or more were administered to 607 (56.3%) of 1079 patients with ES-SCLC. Elderly NSCLC patients received slightly more high-cost treatment than younger patients., Conclusion: Recent treatments cost many times more than conventional chemotherapy. This study revealed that high-cost treatments were widely used in advanced lung cancer and some of high-cost treatments were used despite the lack of clear evidence. Physicians should pay attention to the cost of treatments they use., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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20. First-line nivolumab plus ipilimumab with or without chemotherapy for Japanese patients with non-small cell lung cancer: LIGHT-NING study.
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Imai H, Kijima T, Azuma K, Kishi K, Saito H, Yamaguchi T, Tanizaki J, Yoneshima Y, Fujita K, Watanabe S, Kitazono S, Fukuhara T, Hataji O, Toi Y, Mizutani H, Hamakawa Y, Maemondo M, Ohsugi T, Suzuki K, Horinouchi H, and Ohe Y
- Subjects
- Humans, Male, Aged, Female, Nivolumab adverse effects, Ipilimumab adverse effects, Japan epidemiology, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Lung Neoplasms etiology
- Abstract
Objective: As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited., Methods: LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information., Results: We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0-9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3-4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3-4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2-7.6) and 5.8 (4.3-7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively., Conclusions: LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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21. Distinction of ALK fusion gene- and EGFR mutation-positive lung cancer with tumor markers.
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Akita T, Ariyasu R, Kakuto S, Miyadera K, Kiritani A, Tsugitomi R, Amino Y, Uchibori K, Kitazono S, Yanagitani N, Tasaka S, and Nishio M
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- Humans, Biomarkers, Tumor genetics, Carcinoembryonic Antigen, ErbB Receptors genetics, Mutation, Neoplasm Recurrence, Local, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung pathology, Keratin-19, Lung Neoplasms pathology
- Abstract
Background: It is difficult to predict gene mutations individually based on clinical background alone. Tumor markers may help to predict each gene mutation. Identifying tumor markers that can predict gene mutation will facilitate timely genetic testing and intervention., Methods: We selected 134 cases of advanced or recurrent ALK-positive and 172 cases of advanced or recurrent EGFR-positive lung cancer from our clinical database. The cutoff values for the tumor markers were defined as 5.0 ng/mL or higher for carcinoembryonic antigen (CEA) and 3.5 ng/mL or higher for soluble fragment of cytokeratin 19 (CYFRA21-1) in accordance with the institutional standards. A positive CYFRA21-1:CEA ratio was defined as 0.7 or higher., Results: The CEA-positivity rate was 49% for ALK-positive lung cancers and 73% for EGFR-positive lung cancers, which was significantly different (p < 0.001). The CYFRA21-1 positivity rate was significantly higher in ALK-positive lung cancer (36%) compared with EGFR-positive lung cancer (23%) (p = 0.034). The median CYFRA21-1:CEA ratio was 0.395 for the ALK group, which was significantly higher compared with 0.098 for the EGFR group (p < 0.001). These trends were similar when excluding histology other than adenocarcinoma. The median time-to-treatment failure (TTF) for initial tyrosine kinase inhibitor (TKI) therapy was 308 days for the high CYFRA21-1:CEA ratio group and 617 days for the low CYFRA21-1:CEA ratio group for ALK-positive lung cancer (p = 0.100)., Conclusions: A higher proportion of patients with ALK-positive lung cancer were CYFRA21-1 positive and had higher CYFRA21-1:CEA ratios compared with EGFR-positive lung cancer patients., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)
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- 2024
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22. Efficacy of osimertinib in patients with EGFR-mutation positive non-small cell lung cancer with malignant pleural effusion.
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Kiritani A, Amino Y, Uchibori K, Akita T, Harutani Y, Ogusu S, Tsugitomi R, Manabe R, Ariyasu R, Kitazono S, Yanagitani N, and Nishio M
- Subjects
- Humans, ErbB Receptors genetics, Retrospective Studies, Protein Kinase Inhibitors, Mutation, Neoplasm Recurrence, Local, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Pleural Effusion, Malignant drug therapy, Pleural Effusion, Malignant genetics, Acrylamides, Aniline Compounds, Indoles, Pyrimidines
- Abstract
Background: As an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), osimertinib has emerged as a standard EGFR-mutation positive treatment for non-small cell lung cancer (NSCLC). However, the efficacy of osimertinib for malignant pleural effusion (MPE) remains understudied. This study aimed to evaluate the impact of osimertinib on time to treatment failure (TTF) and overall survival (OS) in patients with EGFR-mutation positive NSCLC, comparing those with and without MPE., Methods: This retrospective analysis included patients with advanced or recurrent NSCLC treated with osimertinib at our hospital between April 2016 and June 2021. TTF was defined as the duration from osimertinib initiation to discontinuation, and OS as the duration until death, irrespective of the reason., Results: Among 229 patients receiving osimertinib, 84 had MPE before administration, 39 acquired EGFR exon20 T790M mutation following previous EGFR-TKI therapy, and 45 were EGFR-TKI-naive. Among EGFR-TKI-naive patients, median TTF was 14.8 and 19.8 months for those with and without MPE, respectively (hazard ratio [HR] 1.40; 95% confidence interval [CI]: 0.90-2.18; p = 0.12). Median OS was 32.0 and 42.0 months for patients with and without MPE, respectively (HR 1.43; 95% CI: 0.86-2.38; p = 0.16). Among patients with T790M mutation, median TTF was 12.3 and 13.1 months for patients with and without MPE, respectively (HR 1.03; 95% CI: 0.69-1.55; p = 0.88). Median OS for patients with and without MPE was 23.2 and 24.7 months, respectively (HR 1.09; 95% CI: 0.72-1.67; p = 0.68)., Conclusion: Among patients with EGFR-mutation positive NSCLC, the evidence of MPE has little effect on survival with osimertinib., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)
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- 2024
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23. Clinical characteristics of patients with KRAS mutation detected by liquid biopsy.
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Amino Y, Low SK, Ninomiya H, Kiritani A, Miyadera K, Kakuto S, Akita T, Tsugitomi R, Ariyasu R, Uchibori K, Kitazono S, Yanagitani N, and Nishio M
- Subjects
- Male, Humans, Proto-Oncogene Proteins p21(ras) genetics, Mutation, Liquid Biopsy, Adenocarcinoma pathology, Lung Neoplasms genetics, Lung Neoplasms pathology, Adenocarcinoma, Mucinous genetics, Adenocarcinoma, Mucinous pathology
- Abstract
Background: KRAS mutation positive lung cancer is known to be clinically characterized by older age, males, and smokers. It is reported to be more common in mucinous adenocarcinoma, but all reports are based on analysis of tissue samples. Recently, blood samples have become available for analysis, suggesting a low detection rate of circulating tumor DNA in histological types, especially mucinous adenocarcinoma. In this study, we investigated the clinical characteristics of KRAS mutation-positive cases in the analysis of blood specimens, as these remain unclear., Methods: The clinical background of patients with KRAS mutation among those who underwent next-generation sequencing (NGS) analysis using blood samples was evaluated., Results: NGS analysis was performed on 214 blood samples. KRAS mutations were detected in blood samples in 33 cases (15.4%), of which 31 cases (14.5%) had a histological pathology diagnosis. Mucinous adenocarcinoma accounted for 28.6% of cases with positive blood and tissue specimens, 10.0% of cases with positive blood specimens only, and 57.1% of cases with positive tissue specimens only. Mucinous adenocarcinoma tended to be less common in cases with positive blood specimens. In KRAS-positive patients with lung metastasis only, only one nonmucinous adenocarcinoma had a positive blood sample, and the others all had mucinous adenocarcinomas with positive tissue samples only., Conclusion: The results showed that the detection rate of KRAS-positive lung cancers detected by blood and tissue samples differs, and that the detection rate of blood samples may be poor, especially in the case of mucinous adenocarcinoma with lung metastases only., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
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- 2023
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24. First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01.
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Shimizu T, Sands J, Yoh K, Spira A, Garon EB, Kitazono S, Johnson ML, Meric-Bernstam F, Tolcher AW, Yamamoto N, Greenberg J, Kawasaki Y, Zebger-Gong H, Kobayashi F, Phillips P, Lisberg AE, and Heist RS
- Subjects
- Adult, Humans, Trophoblasts pathology, Antibodies, Monoclonal, Humanized adverse effects, Antigens, Surface, Carcinoma, Non-Small-Cell Lung drug therapy, Immunoconjugates adverse effects, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Antineoplastic Agents adverse effects
- Abstract
Purpose: This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, and antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate in solid tumors, including advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Adults with locally advanced/metastatic NSCLC received 0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 4, 6, or 8 mg/kg Dato-DXd once every 3 weeks during expansion. Primary end points were safety and tolerability. Secondary end points included objective response rate (ORR), survival, and pharmacokinetics., Results: Two hundred ten patients received Dato-DXd, including 180 in the 4-8 mg/kg dose-expansion cohorts. This population had a median of three prior lines of therapy. The maximum tolerated dose was 8 mg/kg once every 3 weeks; the recommended dose for further development was 6 mg/kg once every 3 weeks. In patients receiving 6 mg/kg (n = 50), median duration on study, including follow-up, and median exposure were 13.3 and 3.5 months, respectively. The most frequent any-grade treatment-emergent adverse events (TEAEs) were nausea (64%), stomatitis (60%), and alopecia (42%). Grade ≥3 TEAEs and treatment-related AEs occurred in 54% and 26% of patients, respectively. Interstitial lung disease adjudicated as drug-related (two grade 2 and one grade 4) occurred in three of 50 patients (6%). The ORR was 26% (95% CI, 14.6 to 40.3), and median duration of response was 10.5 months; median progression-free survival and overall survival were 6.9 months (95% CI, 2.7 to 8.8 months) and 11.4 months (95% CI, 7.1 to 20.6 months), respectively. Responses occurred regardless of TROP2 expression., Conclusion: Promising antitumor activity and a manageable safety profile were seen with Dato-DXd in heavily pretreated patients with advanced NSCLC. Further investigation as first-line combination therapy in advanced NSCLC and as monotherapy in the second-line setting and beyond is ongoing.
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- 2023
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25. Soluble interleukin-2 receptor as a predictive biomarker for poor efficacy of combination treatment with anti-PD-1/PD-L1 antibodies and chemotherapy in non-small cell lung cancer patients.
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Tozuka T, Yanagitani N, Yoshida H, Manabe R, Ogusu S, Tsugitomi R, Sakamoto H, Amino Y, Ariyasu R, Uchibori K, Kitazono S, Seike M, Gemma A, and Nishio M
- Subjects
- Humans, Male, Aged, Female, B7-H1 Antigen metabolism, Biomarkers, Antibodies, Receptors, Interleukin-2, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology
- Abstract
Soluble interleukin-2 receptor (sIL-2R) suppresses effector T-cells. Few studies have assessed serum sIL-2R in patients receiving immunotherapy. We evaluated the association between serum sIL-2R levels and the efficacy of anti-programmed cell death 1/ programmed death-ligand 1 (anti-PD-1/PD-L1) antibody combined with chemotherapy in non-small cell lung cancer (NSCLC) patients. We prospectively enrolled NSCLC patients who received anti-PD-1/PD-L1 antibody combined with platinum-based chemotherapy between 8/2019 and 8/2020 and measured their serum sIL-2R. The patients were divided into high and low sIL-2R groups based on the median of sIL-2R levels at pretreatment. Progression-free survival (PFS) and overall survival (OS) of patients in the high and low sIL-2R groups were compared. The Kaplan-Meier curves of PFS and OS were evaluated using the log-rank test. The multivariate analysis of PFS and OS was performed using the Cox proportional hazard models. Among 54 patients (median age 65, range 34-84), 39 were male and 43 had non-squamous cell carcinoma. The sIL-2R cut-off value was 533 U/mL. Median PFS was 5.1 months (95% CI, 1.8-7.5 months) and 10.1 months (95% CI, 8.3-not reached [NR] months) in the high and low sIL-2R groups (P = 0.007), respectively. Median OS was 10.3 months (95% CI, 4.0-NR months) and NR (95% CI, 10.3-NR months) in the high and low sIL-2R groups (P = 0.005), respectively. Multivariate Cox regression analysis showed that high sIL-2R was significantly associated with shorter PFS and OS. SIL-2R may be a biomarker for the poor efficacy of anti-PD-1/PD-L1 antibody combined with chemotherapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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26. Real-World Outcome Analysis of Patients With Stage IV NSCLC Treated With Tyrosine Kinase and Immune Checkpoint Inhibitors.
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Ariyasu R, Kakuto S, Miyadera K, Akita T, Kiritani A, Tsugitomi R, Amino Y, Uchibori K, Kitazono S, Yanagitani N, and Nishio M
- Abstract
Introduction: Only a few reports have determined whether recently advanced anticancer drugs, particularly next-generation tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), prolong the survival of patients with NSCLC in the real world., Methods: To evaluate the association between recently advanced drugs and patient survival, survival data of 2078 patients with stage IV NSCLC from 1995 to 2022 were analyzed in the present study. The patients were classified into the following six groups in terms of the date of diagnosis: period A, 1995 to 1999; period B, 2000 to 2004; period C, 2005 to 2009; period D, 2010 to 2014; period E, 2015 to 2019; and period F, 2000 to 2022. They were further grouped in terms of EGFR mutation and ALK fusion., Results: The median overall survival (mOS) times were 8.9, 11.0, 13.6, 17.9, and 25.2 months in periods A to E, respectively, and the mOS time was not reached in period F. This time was significantly longer in period E than in period D (25.2 versus 17.9 mo, p < 0.005). Moreover, the mOS times of patients with EGFR mutation, those with ALK fusion, and those without both alterations were significantly longer in period E than in period D (46.0 versus 32.0 mo, p < 0.005; not reached versus 36.2 mo, p = 0.018; 14.6 versus 11.7 mo, p < 0.005). The history of treatment with next-generation TKIs and ICIs was found to be associated with overall survival., Conclusions: The survival of patients with NSCLC was improved from period D to period E, regardless of the presence of driver gene alteration. We found that next-generation TKIs and ICIs may be associated with improvements in overall survival., (© 2023 The Authors.)
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- 2023
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27. Pharmacokinetic and dose-finding study of osimertinib in patients with impaired renal function and low body weight.
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Fujiwara Y, Makihara R, Hase T, Hashimoto N, Naito T, Tsubata Y, Okuno T, Takahashi T, Kobayashi H, Shinno Y, Zenke Y, Ikeda T, Hosomi Y, Watanabe K, Kitazono S, Sakiyama N, Makino Y, and Yamamoto N
- Subjects
- Humans, Aniline Compounds adverse effects, Kidney physiology, Body Weight, Mutation, Protein Kinase Inhibitors adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Renal Insufficiency
- Abstract
The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m
2 ) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30-50 mL/min/1.73 m2 ); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2023
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28. Advances in the treatment of postoperative recurrence of non-small cell lung cancer and their impact on survival in Asian patients.
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Hashimoto K, Ariyasu R, Ichinose J, Matsuura Y, Nakao M, Amino Y, Uchibori K, Kitazono S, Yanagitani N, Okumura S, Nishio M, and Mun M
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- Humans, Anaplastic Lymphoma Kinase genetics, ErbB Receptors genetics, Mutation, Protein Kinase Inhibitors, Retrospective Studies, Asian, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology
- Abstract
Objectives: We investigated the effect of tyrosine kinase inhibitors (TKIs) and immunotherapy on survival after postoperative recurrence of non-small cell lung cancer (NSCLC)., Methods: This single-center retrospective study included patients with NSCLC who underwent lobectomy or more with complete pathological resection between 2008 and 2018 (N = 2254). Median follow-up was 5.1 years. Survival trends and the effect of TKIs/immunotherapy were analyzed using Joinpoint (National Cancer Institute) and Cox regression., Results: In 443 (19.7%) postoperative recurrences, median time to recurrence was 1.1 years; epidermal growth factor receptor mutation (EGFR+), 191 (43.1%); anaplastic lymphoma kinase rearrangement (ALK+), 13 (2.9%); not detected or unknown (ND), 239 (54.0%). In multivariable analysis, age, time to recurrence, adenocarcinoma, symptomatic recurrence, any treatment for recurrence, use of the epidermal growth factor receptor TKI, use of the anaplastic lymphoma kinase TKI, and use of immunotherapy were significant prognostic factors. Survival was significantly better in the EGFR+/ALK+ group than in the ND group (median, 4.7 vs 2.1 years; P < .01). Between 2010 and 2018, 2-year postrecurrence survival improved significantly (annual percentage change [APC], 4.2; 95% CI, 1.5-7.0). In subset analyses, neither change in 2-year survival nor TKI use was significant over time in the EGFR+/ALK+ group, but the ND group experienced significant improvement in 2-year survival (APC, 13.5; 95% CI, 5.4-22.2) and increasing trend in immunotherapy use (APC, 23.0; 95% CI, -5.9 to 60) after 2013., Conclusions: Survival after postoperative recurrence of NSCLC has improved significantly since 2010. Use of immunotherapy in patients without driver mutations may have contributed to that improvement. Prognosis in patients with driver mutations remains favorable with the TKIs introduced before the study period., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2023
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29. Implementation of microsatellite instability testing for the assessment of solid tumors in clinical practice.
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Nakayama I, Shinozaki E, Kawachi H, Sasaki T, Yunokawa M, Tomomatsu J, Yuasa T, Kitazono S, Kobayashi K, Hayakawa K, Ueki A, Takahashi S, and Yamaguchi K
- Subjects
- Humans, Microsatellite Instability, Retrospective Studies, Medical Oncology, Japan, DNA Mismatch Repair, Microsatellite Repeats, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms pathology
- Abstract
Background: In Japan, microsatellite instability (MSI) testing for solid tumors was introduced in clinical practice in December 2018. Although immune checkpoint inhibitors (ICIs) are established standards of care for patients with MSI-high tumors, the status of implementing MSI testing in clinical practice remains unclear., Methods: We retrospectively reviewed the medical records of patients with solid tumors who underwent MSI testing between January 2019 and December 2020 at our institution., Results: In total, 1,052 MSI tests were performed in 1,047 patients. Regardless of specimen volume and condition, the MSI status was successfully determined in 1,041 (99.0%) tests, encompassing 27 tumor types (microsatellite stable [MSS] or MSI-low: n = 991 [95.2%] and MSI-high: n = 50 [4.8%]). Patients whose specimens were fixed with 20% neutral buffered formalin (NBF) and who had specimens with prolonged storage (98.4% and 95.4%) showed lower success rates than those whose specimens were fixed with 10% NBF and who had specimens with nonprolonged storage (100.0% and 99.6%), respectively. The prolonged turnaround time (TAT) in MSI-high cases (median TAT: 24 days) was a critical issue that directly resulted in treatment delay. Of the 50 patients with MSI-high tumors, 24 (48.0%) received ICIs and 34 (68.0%) were referred to the Department of Clinical Genetic Oncology where 6 (12.0%) patients were diagnosed with Lynch syndrome., Conclusions: MSI testing was successfully performed for various types of tumors and specimens in clinical practice. Our study results identified certain issues associated with the clinical implementation of MSI testing, including optimal specimen selection, extended TAT in MSI-high cases, and awareness of hereditary tumors., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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30. Clinical efficacy of amrubicin in patients with small cell lung cancer relapse after first-line treatment including immune checkpoint inhibitors: A retrospective multicenter study (TOPGAN 2021-01).
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Uematsu S, Kitazono S, Tanaka H, Saito R, Kawashima Y, Ohyanagi F, Tozuka T, Ryosuke T, Sakatani T, Horiike A, Yoshizawa T, Saiki M, Tambo Y, Koyama J, Kanazu M, Kudo K, Tsuchiya-Kawano Y, Yanagitani N, and Nishio M
- Subjects
- Humans, Immune Checkpoint Inhibitors pharmacology, Immune Checkpoint Inhibitors therapeutic use, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Treatment Outcome, Recurrence, Lung Neoplasms drug therapy, Lung Neoplasms chemically induced, Carcinoma, Non-Small-Cell Lung drug therapy, Small Cell Lung Carcinoma drug therapy, Antineoplastic Agents therapeutic use
- Abstract
Background: The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however, it is unclear whether the same is applicable for small cell lung cancer (SCLC). We evaluated the efficacy of second-line amrubicin (AMR) following first-line platinum-based chemotherapy and ICI combination therapy (chemo-ICI) in SCLC., Patients and Methods: We retrospectively enrolled consecutive patients with SCLC treated with AMR as a second-line following chemo-ICI as first-line between July 2019 and April 2021 from 16 institutions throughout Japan. We investigated the therapeutic effectiveness, safety, and efficacy-enhancing variables of AMR., Results: Overall, 89 patients treated with AMR after first-line chemo-ICI were analyzed. The overall response rate (ORR) was 29.2% (95% confidence intervals [CI], 20.1-39.8) and median PFS (m PFS) was 2.99 months (95% CI, 2.27-3.65). Patients who relapsed more than 90 days after receiving first-line platinum combination therapy (sensitive relapse) exhibited greater ORR (58.3% vs. 24.7%, p = 0.035) and m PFS (5.03 vs. 2.56 months, p = 0.019) than patients who relapsed in <90 days (refractory relapse). Grade 3 or higher adverse events were mainly hematological toxicity., Conclusions: Our study suggested that the therapeutic effect of AMR was not enhanced after ICI on SCLC. However, AMR may be effective in cases of sensitive relapse after chemo-ICI. There was no increase in severe toxicity associated with AMR after ICI., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
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- 2023
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31. EGFR-TKI re-administration after osimertinib failure in T790M mutation loss cases with re-biopsy.
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Ogusu S, Ariyasu R, Akita T, Kiritani A, Tsugitomi R, Amino Y, Uchibori K, Kitazono S, Yanagitani N, and Nishio M
- Subjects
- Humans, ErbB Receptors genetics, Protein Kinase Inhibitors therapeutic use, Retrospective Studies, Mutation, Aniline Compounds therapeutic use, Biopsy, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Data on the re-administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) after osimertinib failure in patients with T790M-positive non-small cell lung cancer (NSCLC) is limited. EGFR-TKI re-administration efficacy may vary between patients with T790M loss and those with T790M persistent with re-biopsy after osimertinib treatment. Patients who received EGFR-TKI re-administration (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) after osimertinib failure were identified from our database. T790M mutation status before EGFR-TKI re-administration was analyzed via repeat biopsy. We retrospectively evaluated the efficacy of EGFR-TKI re-administration, especially differences according to the T790M mutation status, via repeat biopsy. Until June 2020, 28 patients received EGFR-TKI re-administration and 17 underwent repeat biopsy after osimertinib failure. Patients were divided into three groups, including the T790M loss group, where active mutation persisted and T790M was lost (13/17); T790M remaining group, where both the active mutation and T790M persisted (3/17); and active mutation loss group where both the active mutation and T790M were lost (1/17). The overall response rate (ORR) of EGFR-TKI re-administration in the T790M loss group was 31% and the disease control rate (DCR) was 54%, which were higher than the ORR of 21% and DCR of 43% in the entire patient population. ORR and DCR of the not re-biopsy group were low (9% and 27%, respectively). The therapeutic effect of EGFR-TKI re-administration in patients with T790M-positive NSCLC after osimertinib failure is limited. EGFR-TKI re-administration may be considered in cases of T790M loss after repeat biopsy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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32. Rapid genomic profiling of circulating tumor DNA in non-small cell lung cancer using Oncomine Precision Assay with Genexus™ integrated sequencer.
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Low SK, Ariyasu R, Uchibori K, Hayashi R, Chan HT, Chin YM, Akita T, Harutani Y, Kiritani A, Tsugitomi R, Manabe R, Ogusu S, Amino Y, Kitazono S, Yanagitani N, Nakamura Y, and Nishio M
- Abstract
Background: Genomic profiling of tumors from cancer patients facilitates molecular-guided therapy. The turnaround time is one of important issues to deliver results timely for clinical decisions. The Ion Torrent™ Genexus™ Integrated Sequencer automates all next generation sequencing (NGS) workflows and delivers results within a day., Methods: In this study, we conducted a feasibility study to evaluate the detection rate of genomic alterations from cell-free total nucleic acid (cfTNA, containing cfDNA and cfRNA) of 119 non-small cell lung cancer using Oncomine Precision Assay on Genexus™ Integrated Sequencer. Oncomine Precision Assay (OPA) covers actionable mutations, copy number variations and fusion genes and that are applicable for the selection of targeted therapy. cfTNA isolated from plasma (derived from 14 ml of blood) were subjected to the Genexus system for library construction, templating, sequencing, and data analyses., Results: The sequencing resulted in median overall depth of 35,773× and median molecular coverage of 2,192× with cfTNA input ranged from 11 to 36 ng. Among the 119 samples evaluated, we detected at least one genomic alteration in plasma cfTNA of 79 cases (66%). When comparing to standard-of-care testing, the sensitivity and specificity of mutation detection in non-small cell lung cancer related genes using liquid biopsy with Genexus-OPA ranged between 49-67% and 93-100%, respectively. 59% of actionable mutations, which were present in tumor tissues, were detected by the Genexus- Oncomine Precision Assay using plasma cfTNA. Among the 5 mutations detected from liquid biopsy only, three mutations are of level 1 evidence according to OncoKB database, highlighting the clinical utilities of liquid biopsy in addressing tumor heterogeneity. Extrathoracic metastasis and levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and Carcinoembryonic Antigen (CEA) are found to be associated with increased circulating tumor DNA detection., Conclusions: The Genexus™ Integrated Sequencer system is an automated, accurate NGS system with short turnaround time (TAT) that could assist clinicians to make more timely decision., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-981/coif). SKL serves as a scientific advisor and received honorarium from Cancer Precision Medicine Inc. RA receives personal fees for lectures from AstraZeneca, Chugai Pharmaceutical. KU receives personal fees for lectures from AstraZeneca, Brystol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Novartis, Ono Pharmaceutical, and Takeda Pharmaceutical Company Limited, and for manuscript writing from Chugai-Igakusha, Nankodo Co., Ltd., Nanzando Co., Ltd., Yodosha Co., Ltd. KU’s spouse is an employee of Daiichi Sankyo. RH and YMC are Employees of Cancer Precision Medicine, Inc. NY is a medical advisor of Chugai Pharmaceutical and receives lecture’s fee from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, and Takeda Pharmaceutical Company Limited. YN serves as a scientific advisor of Oncotherapy Science Inc., and possesses stock from Oncotherapy Science Inc. MN receives grants and personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Novartis, Daiichi Sankyo, and Takeda Pharmaceutical Company Limited, personal fees from Boehringer-Ingelheim, Merck Biopharma, Teijin Pharma Limited, and AbbVie. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)
- Published
- 2022
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33. Characteristics of central nervous system progression in non-small cell lung cancer treated with crizotinib or alectinib.
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Sakamoto H, Yanagitani N, Manabe R, Tsugitomi R, Ogusu S, Tozuka T, Yoshida H, Amino Y, Ariyasu R, Uchibori K, Kitazono S, Tasaka S, and Nishio M
- Subjects
- Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase metabolism, Carbazoles administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung metabolism, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms metabolism, Crizotinib administration & dosage, Female, Follow-Up Studies, Humans, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Male, Middle Aged, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local metabolism, Piperidines administration & dosage, Prognosis, Retrospective Studies, Survival Rate, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung pathology, Central Nervous System Neoplasms secondary, Lung Neoplasms pathology, Neoplasm Recurrence, Local pathology
- Abstract
Background: Most patients treated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors for ALK-positive non-small cell lung cancer (NSCLC) develop resistance, leading to metastasis, with progression to the central nervous system (CNS) being a primary concern. Although alectinib has better CNS penetration than crizotinib, patients treated with alectinib also develop CNS progression. CNS metastases more likely occurs during crizotinib treatment due to less blood-brain barrier (BBB) penetration capability than alectinib. CNS progression pattern may be different during crizotinib and alecitinib treatment. Understanding the characteristics of CNS progression is important for developing treatment strategies., Aims: We compared the clinical-radiographic characteristics of CNS metastases among patients undergoing crizotinib and alectinib treatment for ALK-positive NSCLCs., Methods and Results: We retrospectively analyzed the radiographic and clinical characteristics of CNS progression in ALK-positive NSCLC patients treated with crizotinib or alectinib at our hospital between July 2011 and May 2020. CNS and systemic tumor progression were evaluated using computed tomography or magnetic resonance imaging. Fifty-three and 65 patients were treated with crizotinib and alectinib, respectively. Baseline CNS metastasis was observed in 18 and 27 patients in the crizotinib and alectinib groups, respectively. Among the patients in the crizotinib and alectinib groups who developed disease progression, 15/49 (30.6%) and 9/44 (20.5%) had CNS progression, respectively (P = .344). Intra-CNS progression-free survival was significantly longer in the alectinib group than in the crizotinib group (median: 14.0 vs 5.6 months, P = .042). The number of CNS metastases sized ≥3 cm, rate of peritumoral brain edema, and the second progression pattern after treatment continuation was not significantly different between the groups., Conclusion: We observed no significant difference in the clinical-radiographic characteristics of CNS progression between patients undergoing crizotinib and alectinib treatments. Local therapy, including stereotactic radiosurgery, for CNS progression may be suitable and important following alectinib and crizotinib treatment., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)
- Published
- 2021
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34. Minimal Change Disease Associated With Durvalumab.
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Toda MG, Fujii K, Kato A, Yoshifuji A, Komatsu M, Amino Y, Kitazono S, Hashiguchi A, and Ryuzaki M
- Published
- 2021
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