Randomized Phase III Study of Pemetrexed Plus Cisplatin Versus Vinorelbine Plus Cisplatin for Completely Resected Stage II to IIIA Nonsquamous Non–Small-Cell Lung Cancer

2020 ◽  
Vol 38 (19) ◽  
pp. 2187-2196 ◽  
Author(s):  
Hirotsugu Kenmotsu ◽  
Nobuyuki Yamamoto ◽  
Takeharu Yamanaka ◽  
Katsuo Yoshiya ◽  
Toshiaki Takahashi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Stage Ii ◽  
Phase Iii ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Pathologic Stage ◽  
Phase Iii Study ◽  
Nonsquamous Nsclc

PURPOSE To evaluate the efficacy of pemetrexed plus cisplatin versus vinorelbine plus cisplatin as postoperative adjuvant chemotherapy in patients with pathologic stage II-IIIA nonsquamous non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS We performed a randomized, open-label, phase III study at 50 institutions within 7 clinical study groups in Japan. Patients with completely resected pathologic stage II-IIIA (TNM 7th edition) nonsquamous NSCLC were randomly assigned to receive either pemetrexed (500 mg/m2, day 1) plus cisplatin (75 mg/m2, day 1) or vinorelbine (25 mg/m2, days 1 and 8) plus cisplatin (80 mg/m2, day 1) with stratification by sex, age, pathologic stage, EGFR mutation, and institution. These treatments were planned to be given every 3 weeks for 4 cycles. The primary end point was recurrence-free survival in the modified intent-to-treat population, excluding ineligible patients. RESULT Between March 2012 and August 2016, 804 patients were enrolled (402 assigned to vinorelbine plus cisplatin and 402 assigned to pemetrexed plus cisplatin). Of 784 eligible patients, 410 (52%) had stage IIIA disease and 192 (24%) had EGFR-sensitive mutations. At a median follow-up of 45.2 months, median recurrence-free survival was 37.3 months for vinorelbine plus cisplatin and 38.9 months for pemetrexed plus cisplatin, with a hazard ratio of 0.98 (95% CI, 0.81 to 1.20; 1-sided P = .474). Grade 3-4 toxicities reported more frequently for vinorelbine plus cisplatin than for pemetrexed plus cisplatin were febrile neutropenia (11.6% v 0.3%, respectively), neutropenia (81.1% v 22.7%, respectively), and anemia (9.3% v 2.8%, respectively). One treatment-related death occurred in each arm. CONCLUSION Although this study failed to show the superiority of pemetrexed plus cisplatin for patients with resected nonsquamous NSCLC, this regimen showed a better tolerability as adjuvant chemotherapy.

Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non–Small-Cell Lung Cancer With EGFR Mutation (IMPACT)

2021 ◽  
Author(s):  
Hirohito Tada ◽  
Tetsuya Mitsudomi ◽  
Toshihiro Misumi ◽  
Kenji Sugio ◽  
Masahiro Tsuboi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Stage Ii ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Study

PURPOSE To investigate the efficacy of gefitinib as an adjuvant therapy for non–small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252 ), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non–small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

Vinorelbine plus cisplatin versus gefitinib in resected non-small cell lung cancer haboring activating EGFR mutation (WJOG6410L).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7110-TPS7110 ◽  
Author(s):  
Hirohito Tada ◽  
Koji Takeda ◽  
Kazuhiko Nakagawa ◽  
Isamu Okamoto ◽  
Tetsuya Mitsudomi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Stage Ii ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Resected Stage

TPS7110 Background: Vinorelbine plus cisplatin after completely resected stage II-III non-small cell lung cancer (NSCLC) is a standard therapy. Stage IV non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) is quite sensitive to tyrosine kinase inhibitors (TKIs). Three randomized trials demonstrated that gefitinib is superior to platinum based chemotherapy in progression free survival. Retrospective analysis of adjuvant TKIs therapy for patient with resected lung cancer harboring EGFR mutation showed favorable trend toward improvement in disease free survival (DFS) and overall survival (OS). (J Thorac Oncol. 2011;6: 569–575) BR19 comparing adjuvant gefitinib vs. placebo for completely resected NSCLC without any selection of biomarker was closed early and did not show any benefit of adjuvant gefitinib, even in the EGFR mutation positive cohort. The randomized trial in adjuvant therapy with erlotinib vs. placebo for patients with overexpression of EGFR protein has complete enrolment already. We conduct the first randomized phase III trial comparing adjuvant gefitinib with chemotherapy in patients with completely resected stage II-III NSCLC harboring EGFR mutations. Methods: Patients who have undergone complete resection and have EGFR mutation, deletions in exon 19, or L858R point mutation at exon 21 and without T790M mutation are randomly assigned gefitinib 250mg a day for 2 years or vinorelbine 25mg/m2 days 1 and 8, plus cisplatin 80mg/m2 day 1, every 3 weeks for 4 courses. The primary endpoint is DFS and secondary endpoints are OS and safety. On the basis of previous studies, we assume the hazard ratio of DFS is 0.65. To demonstrate this improvement in DFS, 230 patients in total would be needed during 3-year accrual period. This trial has begun from September 12 among 22 institutes in Japan. Until now (January 31. 2012), 13 cases have been enrolled. Five cases were enrolled in latest 1 month.

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