In the Japanese phase III JIPANG trial reported in the Journal of Clinical Oncology, Kenmotsu et al found that adjuvant therapy with pemetrexed/cisplatin did not result in superior recurrence-free survival but was better tolerated than vinorelbine/cisplatin in patients with completely resected stage II to IIIA nonsquamous non–small cell lung cancer (NSCLC).
In the multicenter open-label trial, 804 patients were randomly assigned between March 2012 and August 2016 to receive pemetrexed at 500 mg/m2 on day 1 plus cisplatin at 75 mg/m2 on day 1 (n = 402), or vinorelbine at 25 mg/m2 on days 1 and 8 plus cisplatin at 80 mg/m2 on day 1 (n = 402) every 3 weeks for four cycles. A total of 784 patients, consisting of 389 in the pemetrexed/cisplatin group and 395 in the vinorelbine/cisplatin group, were considered eligible and constituted the modified intent-to-treat population. Among these, 52% had stage IIIA disease and 24% had EGFR-mutant disease. The primary endpoint was recurrence-free survival in the modified intent-to-treat population.
Median follow-up was 45.2 months. Median recurrence-free survival was 38.9 months for patients in the pemetrexed/cisplatin group vs 37.3 months in the vinorelbine/cisplatin group (hazard ratio [HR] = 0.98, P = .474), with 2- and 3-year rates of 58.3% vs 60.7% and 51.1% vs 50.2%, respectively. In post hoc analyses, hazard ratios were: 1.38 (95% confidence interval [CI] = 0.95–1.99) among patients with EGFR-mutant disease and 0.87 (95% CI = 0.69–1.09) in those with wild-type disease (P = .046 for interaction); and 0.90 (95% CI = 0.65–1.23) in stage II and 1.05 (95% CI = 0.82–1.34) in stage IIIA disease (P = .442 for interaction).
Median overall survival was not reached in either group. At time of analysis, 71 patients in the pemetrexed/cisplatin group and 75 patients in the vinorelbine/cisplatin group had died (HR = 0.98, P = .434). Survival at 3 years was 87.2% vs 83.5%.
Grade ≥ 3 adverse events occurred in 47.4% of patients in the pemetrexed/cisplatin group vs 89.4% of the vinorelbine/cisplatin group (P < .01), with grade 3 or 4 events occurring significantly (all P < .05) more frequently in the vinorelbine/cisplatin group, including febrile neutropenia (11.6% vs 0.3%), neutropenia (81.1% vs 22.7%, grade 4 in 56.6% vs 3.3%), anemia (9.3% vs 2.8%), and white blood cell count decrease (51.0% vs 5.9%, grade 4 in 9.3% vs 0.3%). One death in each group was considered treatment-related, consisting of sudden death in one patient receiving vinorelbine/cisplatin and pneumonitis in one patient receiving pemetrexed/cisplatin.
The investigators concluded, “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.”
Hirotsugu Kenmotsu, MD, PhD, of the Division of Thoracic Oncology, Shizuoka Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by staff members of the West Japan Oncology Group Data Center and Pharma-Valley Center and by the Japan Agency for Medical Research and Development. Pemetrexed was provided by Eli Lilly. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.