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

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Clinical trial identification

NCT04035486.

Editorial acknowledgement

The authors would like to acknowledge Jenny Wilkinson, PhD, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

I. Okamoto: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. B.G.M. Hughes: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Pfizer, Eisai, Sanofi; Financial Interests, Personal, Principal Investigator: AstraZeneca, Merck Sharp and Dohme, Bristol Myers Squibb, Roche, Pfizer, BeiGene, Sanofi. S. Ahmed: Financial Interests, Personal, Other, Consulting fee: AstraZeneca; Financial Interests, Personal, Other, Lecture fees: AstraZeneca. K.H.H. Lee: Other, Personal and Institutional, Research Grant: Merck; Other, Personal and Institutional, Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Eli Lilly, AstraZeneca, Yuhan. S. Oizumi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical Co., Ltd., Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Ono Pharmaceutical Co., Ltd., Pfizer, Merck Sharp & Dohme, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical. M. Ahn: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Merck Sharp & Dohme, Merck, Takeda, Ono Pharmaceutical Co., Ltd., Novartis, Lilly, Amgen, Yuhan Pharmaceutical; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Merck Sharp & Dohme, Merck, Takeda, Ono Pharmaceutical Co., Ltd., Novartis, Lilly, Amgen, Yuhan Pharmaceutical, Alpha Pharmaceuticals. Y. Tambo: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Taiho, Merck Sharp & Dohme, Pfizer, Kyowa Kirin. R.K. Li: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, ZPT Amgen, ZPT Eli Lilly, Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Novartis, ZPT Amgen, ZPT Eli Lilly, Pfizer. A. Todd: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Kulkarni: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Institutional, Stocks/Shares: AstraZeneca. N.P. Amin: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Sanofi, Janssen. P.A. Jänne: Financial Interests, Institutional, Research Grant: Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Takeda; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Biocartis, Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Duality Biologics, Eli Lilly, Frontier Medicines, Hongyun Biotechnology, Ignyta, Loxo Oncology, Merus, Mirati Therapeutics Inc., Monte Rosa, Novartis, Pfizer, PUMA, Roche/Genentech, Sanofi, Scorpion Therapeutics, SFJ Pharmaceuticals, Silicon Therapeutics, Takeda, Transcenta, Voronoi, Allorion Therapeutics, Accutar Biotech, AbbVie, Blueprint Medicines; Financial Interests, Personal, Other, Co-inventor on a DFCI patent licensed to Lab Corp.: Patent; Financial Interests, Personal, Royalties, DFCI owned IP licensed to Lab Corp.: Intellectual Property. All other authors have declared no conflicts of interest.