Randomized Pii of Concurrent Vs Sequential Alternating Gefitinib and Chemotherapy in Egfr-Mutant Nsclc: Nej005/Tcog0902

Abstract

Background: The first‐line combination of an EGFR‐TKI plus platinum‐based doublet chemotherapy has yet to be sufficiently evaluated for patients with EGFR‐mutant NSCLC. This randomized phase II trial was designed to identify an effective combined regimen of gefitinib (G) plus carboplatin/pemetrexed (CP) for subsequent use in phase III study. Methods: Chemotherapy‐naïve patients with advanced non‐squamous EGFR‐mutated NSCLC were randomly assigned to receive either a concurrent regimen (C group) or a sequential alternating regimen (S group). Patients in the C group received concurrent G (250 mg daily) and CP (AUC = 6 and 500 mg/m2, day 1) of a 3‐week cycle for 6 cycles, followed by concurrent G and P maintenance. Patients in the S group initially received G (days 1 to 28) and then CP (day 29 and 51); the cycle was repeated for 3 cycles, followed by alternating G and P maintenance. The primary endpoint was progression‐free survival (PFS). Results: All 80 patients enrolled were evaluable for efficacy. Median PFS was 17.2 months in the C group and 15.1 months in the S group (p = 0.41). Although overall survival data are immature (with a median follow‐up time of 24.6 months, 10 and 19 death events), median survival times were not reached in the C group, and were 30.0 months in the S group (p = 0.049). Response rates were similar in both groups (87.8% in the C group and 82.1% in the S group). The most common grade 3 or greater adverse events were neutropenia (48.8% and 46.2%), thrombocytopenia (41.5% and 28.2%), and anemia (34.1% and.12.8%). G‐related skin rash or diarrhea was not severe, and interstitial lung disease was not frequent (5% of all patients). No treatment‐related deaths occurred. Conclusion: This is the first randomized study to investigate the efficacy of a combination of EGFR‐TKI and chemotherapy in the EGFR‐mutated setting. Both regimens had promising efficacy with predictable toxicities, although concurrent regimens might provide better overall survival.