4O First-line (1L) osimertinib (osi) ± platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: FLAURA2 post-progression outcomes

Abstract

Osi, a third-generation, central nervous system-active EGFR-tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. In the Phase 3 FLAURA2 study (NCT04035486), 1L osi + platinum-pemetrexed chemotherapy (CTx) significantly improved progression-free survival (PFS) vs osi alone in patients (pts) with EGFRm advanced NSCLC (HR 0.62; 95% CI 0.49, 0.79; p<0.001).1 Here we report post-progression outcomes, including updated overall survival (OS), from FLAURA2. Adult pts with treatment-naïve EGFRm (Exon 19 deletion/L858R) advanced NSCLC and WHO performance status 0/1 received osi 80 mg once daily (QD) + CTx (pemetrexed + cisplatin or carboplatin for 4 cycles every 3 weeks [Q3W]), then osi 80 mg QD + pemetrexed Q3W, or osi 80 mg QD monotherapy until progression/discontinuation criterion. Subsequent therapy (tx) was per investigator choice. Secondary endpoints included time from randomisation to first subsequent tx (TFST), time to second progression (PFS2), time to second subsequent tx (TSST) and OS. Data cutoff (DCO): 3 Apr 2023. We report a second interim analysis (IA) of updated OS (DCO: 8 Jan 2024). At primary DCO (3 Apr 2023), 123/279 (44%) vs 151/278 (54%) pts had discontinued osi + CTx vs osi. Among these pts, 57/123 (46%; osi + CTx) vs 91/151 (60%; osi) began a FST, most commonly CTx in 37/57 (65%) vs 75/91 (82%) pts. TFST, PFS2,1 and TSST HR (95% CI) were 0.73 (0.56, 0.94), 0.70 (0.52, 0.93) and 0.69 (0.51, 0.93), respectively. While OS results remained immature and statistical significance was not reached at the second IA analysis (41% maturity; DCO: 8 Jan 2024), a trend towards OS benefit was observed. Median OS was not reached (95% CI 38.0, not calculable [NC]) with osi + CTx and 36.7 months (95% CI 33.2, NC) with osi; OS HR was 0.75 (95% CI 0.57, 0.97). OS was consistent across predefined subgroups. These FLAURA2 post-progression results demonstrate that 1L osi + CTx provides clinical benefit beyond initial progression vs osi for pts with EGFRm advanced NSCLC, with updated OS data showing an encouraging trend towards OS benefit. 1. Planchard et al. NEJM 2023;389:1935–48.