Randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine /cisplatin (Vnr/Cis) for completely resected stage II-IIIA non-squamous non-small-cell lung cancer (Ns-NSCLC): The JIPANG study.

Abstract

8501 Background: Although previous trials demonstrated the efficacy and safety of postoperative cisplatin–based adjuvant chemotherapy for resected NSCLC, no phase III study has so far evaluated Pem/Cis in this population. Methods: Patients with completely resected pathological stage II-IIIA Ns-NSCLC were randomized in a 1:1 ratio to receive either Pem (500 mg/m2, day 1)/Cis (75 mg/m2, day 1) or vinorelbine (Vnr) (25 mg/m2, days 1 and 8)/Cis (80 mg/m2, day 1), and stratified according to sex, age, pathologic stage, EGFR mutation status and institution. The primary endpoint was recurrence-free survival (RFS), and, the planned sample size was 800 patients in total to detect the superiority of Pem/Cis over Vnr/Cis (Trial Identifier, UMIN000006737). Results: Between March 2012 and August 2016, 804 patients were randomized. Of 784 for the efficacy analysis (389 in Pem/Cis and 395 in Vnr/Cis), median age was 65/65 years; stage IIIA 52/52%; Adenocarcinoma, 96/96%; and EGFR mutation, 24/25%. With a median follow-up of 45.2 months (mo), median RFS was 38.9mo in Pem/Cis and 37.3mo in Vnr/Cis with a hazard ratio (HR) of 0.98 (95% CI, 0.81—1.20; log-rank test, P= 0.948), whereas HRs in patients with and without EGFR mutations were 1.38 (95% CI, 0.95—1.99) and 0.87 (95% CI, 0.69—1.09), respectively (Interaction, P= 0.046). Overall survival rate at 3 years was 83.5% versus 87.2% with a HR of 0.98 (95% CI, 0.71—1.35). Incidences of grade 3 or 4 febrile neutropenia (0.3/11.6%, P< 0.001), neutropenia (22.8/81.1%, P< 0.001), and anemia (2.8/9.3%, P< 0.001); any grade alopecia (12.8/30.1%, P< 0.001). One treatment-related death was observed in each arm. Rates of treatment completions were 87.9% (Pem/Cis) and 72.7% (Vnr/Cis), respectively (P < 0.001). Conclusions: Although this phase III study did not meet the primary endpoint, Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability as postoperative adjuvant chemotherapy for Ns-NSCLC patients. A significant interaction for RFS was found between treatment and EGFR mutation status. Clinical trial information: UMIN000006737.