Dr Jänne on OS Benefit With Osimertinib Plus Chemo by Poor Prognostic Factors in EGFR+ NSCLC

"The study demonstrated that regardless of the presence or absence of clinical or molecular poor prognostic features, [there was] longer survival with the combination of osimertinib and platinum [chemotherapy] plus pemetrexed compared with osimertinib alone."

Pasi A. Jänne, MD, PhD, senior vice president for Translational Medicine, director of the Belfer Center for Applied Cancer Science, director of the Chen-Huang Center for EGFRMutant Lung Cancers, a senior physician, and the David M. Livingston, MD, Chair at Dana-Farber Cancer Institute; as well as a professor of medicine at Harvard Medical School, discussed updated data from an exploratory analysis of overall survival (OS) in poor prognostic subgroups in the phase 3 FLAURA2 trial (NCT04035486) which evaluated osimertinib (Tagrisso) with or without carboplatin and pemetrexed for patients with metastatic EGFR-mutated non–small cell lung cancer (NSCLC).

Findings presented at the 2025 ESMO Congress showed that an overall survival (OS) benefit favoring the combination (n = 279) vs osimertinib monotherapy (n = 278) was consistently observed across each prognostic subgroup evaluated, including those with central nervous system (CNS) metastases, EGFR exon 21 L858R mutations, plasma-detectable EGFR mutations, and TP53 alterations.

In patients presenting with baseline CNS metastases, median OS reached 40.9 months with osimertinib plus chemotherapy compared with 29.7 months for monotherapy (HR 0.72; 95% CI, 0.52-0.99). Both major EGFR mutation subtypes also derived benefit. For those with the L858R mutation, the median OS was 38.1 months vs 32.4 months (HR, 0.76; 95% CI, 0.55-1.07), while median OS was not reached (NR) vs 43.0 months for the exon 19 deletion group (HR, 0.76; 95% CI, 0.56-1.02).

Consistent benefit was also observed across molecular profiles. Patients harboring TP53 alterations saw OS improve to 51.1 months vs 43.1 months (HR, 0.71; 95% CI, 0.40-1.27). Similarly, those with detectable plasma EGFR mutations achieved a median OS of 38.4 months vs 32.5 months (HR, 0.79; 95% CI, 0.60-1.03).

No new safety signals were reported, confirming that adding chemotherapy did not compromise the established tolerability profile of osimertinib. Janne concluded that these compelling data reinforce the combination of osimertinib plus chemotherapy as a first-line standard of care in this setting.

Disclosures: Jänne reported serving on an advisory board or committee for AstraZeneca, Mirati Therapeutics, Boehringer Ingelheim, Plizer, Roche/Genentech, Chugai, El Lilly, Ignyta, Takeda, Novartis, Voronoi, SFJ Pharmaceuticals, Biocartis, LOXO Oncology, PUMA, Sanofi, Transcenta, Daichi Sankyo, Bayer, Silicon Therapeutics, AbbVie, Monte Rosa, Merus, Allorion Therapeutics, Accutar Biotech, Scorpion Therapeutics, Merus, Frontier Medicines, Hongyun Biotechnology, Duality Biologics, Blueprint Medicines, Dizal Pharmaceuticals, GSK, Tolremo, Myris Therapeutics, and Bristol Myers Squibb; and receiving grants or contracts from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Takeda, PUMA, Astellas Pharmaceuticals, and Daiichi Sankyo. He also is the co-inventor of the Dana-Farber Cancer Institute (DFCI)–owned patent on EGFR mutations licensed to Lab Corp, and he reported royalties on DFCI-owned intellectual property on EGFR mutations licensed to Lab Corp.

Reference

Jänne PA, Planchard D, Kobayashi K, et al. FLAURA2: exploratory overall survival analyses in patients with poorer prognostic factors treated with osimertinib ± platinum-pemetrexed as first-line treatment for EGFR-mutated advanced NSCLC. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA77.