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Abstract: Purpose: In a large multicenter international phase III study (CA031) of nab-paclitaxel (nab-P, 130nm albumin-bound paclitaxel particles)+carboplatin (C) vs solvent-based paclitaxel (sb-P)+C, conducted in 6 countries including Japan, nab-PC produced significantly higher overall response rate (ORR), primary end point compared with sb-PC, and acceptable safety profile. The aim of this analysis was to evaluate the efficacy and tolerability of nab-PC vs sb-PC in Japanese patients with advanced non-small-cell lung cancer (NSCLC) who were enrolled in the CA031 study. Patients and methods: In the CA031 study, a total of 1052 patients were randomized to receive either nab-P 100mg/m2 weekly or sb-P 200mg/m2 every 3 weeks both in combination with C at area under the concentration-time curve (AUC)=6 on day 1 of each 3-week cycle. This analysis included 149 Japanese patients with previously untreated stage IIIB or IV NSCLC. Results: The baseline and histologic characteristics of patients were well balanced between the two arms. ORR was higher with nab-PC vs sb-PC (35% vs 27%; response rate ratio=1.318). Progression-free survival (median 6.9 vs 5.6 months; hazard ratio [HR]=0.845) and overall survival (median 16.7 vs 15.9 months; HR=0.930) were better with nab-PC vs sb-PC. Of the grade ≥3 treatment-related adverse events, anemia and thrombocytopenia were more common in nab-PC arm, but sensory neuropathy was less common. Conclusion: The nab-PC treatment yielded promising results regarding the efficacy endpoint, and it was generally well tolerated as first-line therapy for Japanese patients with advanced NSCLC. [Copyright &y& Elsevier]

Lessons Learned: Updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel and concurrent radiotherapy were collected.In the group of 58 patients who were enrolled at 14 institutions in Japan, the median overall survival was not reached and the 2‐year overall survival rate was 66.1% (95% confidence interval, 52.1%–76.8%).Results reveal encouraging feasibility and activity for this regimen. Background: We report the updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel (nab‐P/C) and concurrent radiotherapy (CRT) in patients with locally advanced non‐small cell lung cancer (NSCLC). Methods: Individuals between 20 and 74 years of age with unresectable NSCLC of stage IIIA or IIIB and a performance status of 0 or 1 were eligible for the study. Patients received weekly nab‐paclitaxel at 50 mg/m2 for 6 weeks together with weekly carboplatin at an area under the curve (AUC) of 2 mg/ml/min and concurrent radiotherapy with 60 Gy in 30 fractions. This concurrent phase was followed by a consolidation phase consisting of two 3‐week cycles of nab‐paclitaxel (100 mg/m2 on days 1, 8, and 15) plus carboplatin (AUC of 6 on day 1). After the treatment, patients were observed off therapy. The primary endpoint of the phase II part of the study was progression‐free survival (PFS). Results: Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. At the median follow‐up time of 26.0 months (range, 4.0–49.6 months), the median overall survival (OS) was not reached (95% confidence interval [CI], 25.3 months to not reached) and the 2‐year OS rate was 66.1% (95% CI, 52.1%–76.8%). The median PFS was 11.8 months (95% CI, 8.2–21.0 months), and the 2‐year PFS rate was 35.9% (95% CI, 23.1%–48.9%). Subgroup analysis according to tumor histology or patient age revealed no differences in median PFS or OS. Long‐term follow‐up of toxicities did not identify new safety signals, and no treatment‐related deaths occurred during the study period. Conclusion: Concurrent chemoradiation with nab‐P/C was safe and provided a long‐term survival benefit for patients with locally advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: MET exon 14 skipping mutations occur in 3–4% and MET high amplifications occur in < 1% of patients with non-small-cell lung cancer (NSCLC). Crizotinib, a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 tyrosine kinases, has shown activity in cancer models with various types of MET activation. Methods: The Co-MET study is a single-arm phase 2 trial to assess the safety and efficacy of crizotinib in MET inhibitor-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy number of ≥ 7 (cohort 2). The primary endpoint was the objective response rate (ORR) per RECIST v1.1 by independent radiology review in cohort 1. The key secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 28 patients (23 in cohort 1 and 5 in cohort 2) were enrolled between March 2018 and February 2020. The primary endpoint was met as the ORR (90% confidence interval: CI) in cohort 1 was 38.1% (20.6–58.3). Median DoR, PFS, and OS (95% CI) were 7.6 (1.9-NE), 5.7 (2.1–11.3), 9.1 (4.0–19.9) months, respectively, in cohort 1. ORR in cohort 2 was 40.0% (18.9–92.4). The safety signals were generally consistent with the known safety profile of crizotinib. Conclusions: Crizotinib showed a clinical activity similar to that of tepotinib and capmatinib in patients with NSCLC harboring MET exon 14 skipping mutations. Clinical trial information: UMIN000031623. [ABSTRACT FROM AUTHOR]

• Follow-up data from the REMORA study showed median overall survival of 28.3 months. • Higher relative dose intensity at 8 weeks may be associated with improved outcomes. • Median overall survival was higher at ≥ 75 % relative dose intensity at 8 weeks. • No new safety concerns or treatment-related deaths were reported for lenvatinib. The main objective of this report was to detail the long-term follow-up data from the REMORA study, which investigated the safety and efficacy of lenvatinib in patients with thymic carcinoma. In addition, an exploratory analysis of the association between relative dose intensity (RDI) and the efficacy of lenvatinib is presented. The single-arm, open-label, phase 2 REMORA study was conducted at eight Japanese institutions. Forty-two patients received oral lenvatinib 24 mg once daily in 4-week cycles until the occurrence of intolerable adverse events or disease progression. The REMORA long-term follow-up data were evaluated, including overall survival (OS). RDI was calculated by dividing the actual dose administered to the patient by the standard recommended dose. This trial is registered on JMACCT (JMA-IIA00285) and on UMIN-CTR (UMIN000026777). The updated median OS was 28.3 months (95 % confidence interval [CI]: 17.1–34.0 months), and the OS rate at 36 months was 35.7 % (95 % CI: 21.7 %–49.9 %). When grouped by RDI of lenvatinib, the median OS was 38.5 months (95 % CI: 31.2–not estimable) in patients with ≥ 75 % RDI and 17.3 months (95 % CI: 13.4–26.2 months) in patients with < 75 % RDI (hazard ratio 0.46 [95 % CI: 0.22–0.98]; P = 0.0406) at 8 weeks. Patients who maintained their lenvatinib dose over 8 weeks had a higher objective response rate than patients whose doses were reduced (75.0 % vs 29.4 %; P = 0.0379). No new safety concerns or treatment-related deaths were reported, and lenvatinib had a tolerable safety profile. This follow-up report updated OS in patients with metastatic or recurrent thymic carcinoma. A higher RDI of lenvatinib at 8 weeks could be associated with improved outcomes. [ABSTRACT FROM AUTHOR]

• RET fusion is a key oncogenic alteration in non-small cell lung cancer. • Vandetanib is an oral multikinase inhibitors with RET kinase activity. • Vandetanib has a clinically meaningful efficacy for RET-rearranged lung cancer. • Multikinase inhibitors lead to off-target adverse events not related to RET. • RET-selective inhibitors have improved efficacy and favorable toxicity profile. The LURET phase II study evaluated the efficacy and safety of the multikinase inhibitor vandetanib in patients with previously treated RET -rearranged advanced non-small cell lung cancer (NSCLC). Among the eligible patients included in the primary analysis, the objective response rate met the primary endpoint (53 %, 90 % confidence interval [CI]: 31–74). Here, we report final survival outcomes of the LURET study. Nineteen patients with previously treated RET -rearranged advanced NSCLC continuously received 300 mg of oral vandetanib daily. This final analysis provides updated data on progression-free survival (PFS), overall survival (OS) and safety. This study was registered with UMIN-CTR (number UMIN 000010095). Among the 19 patients in the intention-to-treat population, 42 % had been heavily treated with 3 or more prior chemotherapy regimens. The median PFS was 6.5 months (95 % CI, 3.9–9.3) as determined by an independent radiology review committee. The median OS was 13.5 months (95 % CI, 9.8–28.1) and the overall survival rate at 12 months was 52.6 % (95 % CI 28.7–71.9). The most common adverse events were hypertension (84.2 %), diarrhea (78.9 %), and rash acneiform (63.2 %). Overall, 11 patients (57.9 %) had adverse events leading to a dose reduction, although the safety profile was consistent with that reported in previous studies. Our results indicated that vandetanib enabled a prolonged and clinically meaningful PFS and OS in patients with previously treated RET -rearranged advanced NSCLC at the updated final analysis. The safety profile was consistent with that reported in previous studies, although most of the patients experienced off-target adverse events besides RET. [ABSTRACT FROM AUTHOR]

Objectives Drug-induced interstitial lung disease (ILD) is often associated with high mortality; however it is difficult to predict and manage. we examined the clinical findings and imaging characteristics of nivolumab induced ILD reported in the two phase II studies patients with recurrent or advanced non-small-cell lung cancer. Materials and methods We examined the clinical findings and imaging characteristics of all cases of ILD reported in two phase II trials of nivolumab, an anti-programmed death-1 antibody, in Japanese patients with recurrent or advanced non-small-cell lung cancer. These studies are registered with the Japan Pharmaceutical Information Center, numbers JapicCTI-132072, JapicCTI-132073. Results Eight (7.2%; two with squamous cell carcinoma, six with non-squamous cell carcinoma) of the 111 patients included in these two studies experienced ILD, and a causal relationship with nivolumab could not be ruled out in any of them. ILD of ≥grade 3 severity was found in four patients (3.6%), and ILD was considered a serious treatment-related adverse event in seven patients (6.3%). All of the patients who experienced ILD were male and had a history of smoking, with a median age of 65 years (range 52–78 years). In seven of the eight patients who experienced ILD, their events were rapidly resolving or resolved spontaneously or with steroid therapy; one patient died of respiratory failure without resolution of ILD, after docetaxel treatment was initiated following nivolumab discontinuation. Chest computed tomography images for the seven patients with resolving or resolution of ILD showed a pattern of organizing pneumonia or nonspecific interstitial pneumonia without traction bronchiectasis, while the patient who died had traction bronchiectasis. Conclusion Although the risk factors for nivolumab-induced ILD were not identified, careful monitoring including imaging examinations is important in preventing the worsening of ILD in patients receiving nivolumab. [ABSTRACT FROM AUTHOR]

Objectives TAS-102 is an oral combination treatment comprised of an antimetabolite, trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, at a molar ratio of 1:0.5. This antimetabolite has demonstrated efficacy in clinical trials, including a global phase 3 trial in metastatic colorectal cancer. As this agent has shown activity greater than cisplatin in small cell lung cancer xenograft mouse models, the objective of this study was to evaluate TAS-102 in the second-line treatment of small cell lung cancer. Methods This was a multicenter, open-label, two-arm, randomized phase 2 study designed to compare oral TAS-102 (35 mg/m 2 /dose twice daily) versus control (topotecan or amrubicin). Patients requiring second-line chemotherapy for treatment of small cell lung cancer, either refractory or sensitive to frontline platinum-based chemotherapy, were enrolled. Results Eighteen patients were enrolled. Eight of nine patients receiving TAS-102 discontinued treatment due to progressive disease and one patient died due to clinical progression during the safety follow-up. Unplanned interim futility considerations were made, and the study was terminated early because it was unlikely that superiority of TAS-102 versus comparator could be demonstrated. Six control patients discontinued therapy due to progressive disease and one due to an adverse event. Median progression-free survival was 1.4 months (range 0.9–1.8) versus 2.7 months (range 1.0–6.8) for TAS-102 and control, respectively, with a hazard ratio of 3.76 (80% CI, 1.68–8.40) favoring control. The most common adverse events with TAS-102 were neutropenia, diarrhea, anemia, anorexia, and fatigue, each in three patients. Conclusion TAS-102 showed no evidence of activity in second-line small cell lung cancer. [ABSTRACT FROM AUTHOR]

• Particle therapy for patients with operable early-stage lung cancer has demonstrated good progression free and overall survival. • Toxicity was very mild, with Grade 3 toxicity occurring in 1.5 % of patients. • Type of particle therapy had no effect on overall survival or progression free survival. To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. A total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7–49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %–85.5 %) and OS was 92.5 % (95 % CI: 89.3 %–95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery. [ABSTRACT FROM AUTHOR]