Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009).

9005 Background: Although EGFR-TKI alone has been a standard first-line treatment for pts with advanced NSCLC with EGFR mutations, our phase II study (NEJ005) showed promising efficacy of GCP. NEJ009, an open-label, randomized phase III study, was conducted to evaluate the superiority of GCP vs G in progression-free survival (PFS), PFS2, and overall survival (OS). Methods: Pts with newly diagnosed stage III/IV/ recurrent NSCLC harboring an EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized 1:1 to G 250 mg PO QD or GCP (G 250mg PO QD combined with carboplatin AUC 5 + pemetrexed 500mg/m2, every 3 weeks). The primary endpoints consisting of PFS, PFS2, and OS were sequentially analyzed according to a preplanned gate-keeping method. Secondary endpoints included objective response rate, safety, and quality of life. Results: In September 2017, a preplanned required number of events of PFS2 was observed. The ITT population included 344 pts with baseline characteristics fairly well balanced between the arms. Although GCP demonstrated significantly better PFS compared to G, there was no difference in PFS2 between the arms as below. Additional OS analysis (G:101 events vs GCP:83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR:0.695, p = 0.013). Conclusions: NEJ009 was the first phase III study which evaluated the efficacy of a combination of EGFR-TKI and platinum doublet chemotherapy in untreated advanced NSCLC pts with EGFR mutations. Although GCP regimen failed to demonstrate its superiority in PFS2, it may increase long survivors. ITT Population GCP (N = 169) G (N = 172) Median (months) Median (months) HR PFS 20.9 11.2 0.493 [95%CI: 18.0, 24.2] [95%CI: 9.0, 13.4] [95%CI: 0.390, 0.623] P < 0.001 PFS2 20.9 21.1 0.891 [95%CI: 18.0, 24.2] [95%CI: 17.9, 24.9] [95%CI: 0.708, 1.122] P = 0.806.