1240P - Randomized phase 2 trial of gefitinib with and without pemetrexed as first-line therapy in East Asian patients with advanced, epidermal growth factor receptor (EGFR) mutation-positive (mt+), nonsquamous (NS) non-small cell lung cancer (NSCLC): Translational research and interim overall survival (OS)

Abstract

The primary analysis of this open-label, randomized, multicenter, phase 2 study found significantly longer progression-free survival (PFS) for pemetrexed plus gefitinib (P + G) vs gefitinib alone (G) in 191 East Asian patients with EGFR mt+ NS NSCLC (adjusted hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.48-0.96; P = 0.029). Translational research, interim OS data and updated safety results are reported. Treatment-naive patients with advanced, EGFR mt+ (local laboratory testing), NS NSCLC were randomized (2:1) to receive P + G (pemetrexed 500 mg/m2, Day 1 of 21-day cycles plus gefitinib 250 mg/day; n = 126) or G (gefitinib 250 mg/day; n = 65). Mandatory pretreatment tissue samples were assayed for EGFR mutations by central evaluation (CE) (n = 159) and thymidylate synthase (TS) by immunohistochemistry (n = 146). OS in the intention-to treat (ITT) population and correlation of biomarkers with clinical outcomes were analyzed by adjusted Cox regression. By CE, 149/159 patients (93.7%) were EGFR mt+. In the CE+ population, PFS was longer for P + G (n = 96) vs G (n = 53) (HR: 0.72; 95% CI: 0.48-1.06; P = 0.093), consistent with the primary analysis based on local testing. In patients with low (n = 67) and high (n = 79) TS expression, the PFS HR was 0.47 (95% CI: 0.26-0.87) and 0.83 (95% CI: 0.47-1.46), respectively; the interaction effect was not statistically significant (P = 0.177). At the interim OS analysis (80 events, 58% censoring), OS was not significantly different for P + G vs G (HR: 0.79; 95% CI: 0.49-1.28; P = 0.342). Postdiscontinuation systemic therapy was common (P + G: 62.7%; G: 72.3%). The incidence of grade 3/4 drug-related adverse events was significantly (P = 0.002) higher for P + G (42.9%) vs G (20.0%). The PFS HR for the CE+ population was consistent with the primary ITT analysis. No significant interaction effects were seen for TS. At this interim analysis, there was no statistical difference in OS for P + G vs G. Final OS analyses will be reported when 130 events have occurred.