Dr Jänne on the Design of the FLAURA2 Trial of Osimertinib Plus Chemotherapy in EGFR+ NSCLC

“Prior data [showed] that the combination of chemotherapy and osimertinib improved PFS and OS compared with single-agent osimertinib in patients with [EGFR-mutant NSCLC.”

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 EGFR Mutant 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 the design of the phase 3 FLAURA2 trial (NCT04035486) in EGFR-mutated non–small cell lung cancer (NSCLC).

FLAURA2 was a randomized trial that evaluated osimertinib (Tagrisso) with or without carboplatin and pemetrexed for the first-line treatment of patients with metastatic EGFR-mutated NSCLC, Jänne began. In the investigational arm, patients received oral osimertinib at 80 mg once daily plus 4 cycles of chemotherapy with pemetrexed and a platinum-based agent; maintenance osimertinib plus pemetrexed were given in the investigational arm after induction therapy, he noted.

The primary end point was investigator-assessed progression-free survival (PFS) per RECIST 1.1 criteria. Overall survival (OS) served as the study’s key secondary end point.

During the 2025 ESMO Congress, Jänne presented data from an exploratory OS analysis of FLAURA2, which included patients with poorer prognostic factors. Of note, prior data from FLAURA2 supported the February 2024 FDA approval of osimertinib plus platinum-based chemotherapy in patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. The findings demonstrated that patients who received the combination achieved significant PFS (HR, 0.62; 95% CI, 0.49-0.79; 2-sided P < .0001) and OS benefits (HR, 0.77; 95% CI, 0.61-0.96; P = .02) vs osimertinib alone, Jänne concluded.

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.