There are insufficient data evaluating the efficacy of a first-line regimen consisting of an EGFR-TKI plus platinum-based doublet chemotherapy in EGFR-mutant (mut) NSCLC. In the NEJ005/TCOG0902 study, 80 chemotherapy-naïve patients with advanced, nonsquamous EGFR-mut NSCLC were randomized to 2 different regimens comprised of gefitinib (G) plus carboplatin/pemetrexed (CP) (Oizumi S, et al. ASCO 2014. Abstract 8016). The patients received G + CP concurrently (C group) or in a sequential and alternating regimen (S group). Patients in the S group initially received G on days 1 to 28, and then CP on days 29 and 51, repeated for 3 cycles. The primary end point of the study was progression-free survival (PFS). Median PFS was 17.2 months in the C group and 15.1 months in the S group (P = .41). At a median follow-up of 24.6 months, median overall survival had not been reached in the C group versus 30 months in the S group (P = .049). Overall response rates were similar among the 2 groups (88% and 82% in the C and S groups, respectively). The most common grade 3/4 adverse events were cytopenias, occurring at a higher frequency in the C group than in the S group. This was the first randomized study to investigate the efficacy and safety of the combination of an EGFR-TKI plus CP as first-line therapy of advanced EGFR-mut NSCLC. It appears that treating with this combination concurrently rather than sequentially may provide better outcomes. A flaw in the design of this study was that it did not include a CP comparator group; we must rely on historical data on combination chemotherapy to evaluate the true value of this novel combination.
