Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes

Abstract

Introduction: In the FLAURA PhIII study, the 3. generation EGFR-TKI osimertinib significantly improved PFS vs SoC EGFR-TKIs in pts with previously untreated EGFRm advanced NSCLC (HR 0.46; p < 0.001). Interim OS data was encouraging but not formally statistically significant (HR 0.63; p = 0.007). Here we report exploratory post-progression outcomes (PPO). Method(s): Pts were randomised 1:1 to receive osimertinib (80 mg) or SoC (gefitinib 250 mg or erlotinib 150 mg). Treatment beyond disease progression was allowed if the investigator judged continued clinical benefit; investigators determined subsequent therapy. Pts receiving SoC could cross over to osimertinib after objective disease progression with documented T790M-positive mutation status. Result(s): Globally 556 pts (Germany 16 pts) were randomised. At data cutoff, 138/279 (49%) and 213/277 (77%) pts discontinued osimertinib and SoC, respectively; 82 (29%) and 129 (47%) received a subsequent treatment: EGFR-TKI-containing, 29 (10%) and 97 (35%; 55 [20%] osimertinib); Pt CTx-containing, 46 (16%) and 27 (10%). Median time (mths) to discontinuation of study treatment or death: osimertinib 20.8 (95% CI 17.2, 24.1) vs SoC 11.5 (10.3, 12.8). Median time (mths) to discontinuation of any EGFR-TKI or death: osimertinib 23.0 (19.5, NC) vs SoC 16.0 (14.8, 18.6). All PPO favoured osimertinib (Table). Conclusion(s): PFS benefit with osimertinib was preserved throughout time-to-event post-progression endpoints. Step-wise increase of the statistically significant HRs (PFS 0.46, TFST 0.51, PFS2 0.58, TSST 0.60) provides confidence in the interim OS data. (Table Presented) .