Dr Jänne on Selecting a Combination Regimen in First-Line EGFR+ NSCLC

“[Selecting a combination regimen] is an informed decision-making [process including] the patient. [We need to] let them know what can be achieved clinically with a combination treatment while at the same time explaining the added cost in terms of adverse effects and inconvenience.”

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 factors that he considers when selecting a frontline combination regimen for the treatment of patients with EGFR-mutated non–small cell lung cancer (NSCLC).

During the 2025 ESMO Congress, Jänne presented data from an exploratory analysis of the phase 3 FLAURA2 trial (NCT04035486) which demonstrated that an overall survival (OS) benefit was observed with frontline osimertinib (Tagrisso) plus chemotherapy vs osimertinib monotherapy in patients with EGFR-mutated NSCLC regardless of the presence of poorer prognostic factors. These included the presence of central nervous system metastases, EGFR exon 21 L858R mutations, plasma-detectable EGFR mutations, and TP53 alterations.

Jänne noted that the results produced in the FLAURA2 trial as well as those seen in the phase 3 MARIPOSA trial (NCT04487080) of amivantamab (Rybrevant) plus lazertinib (Lazcluze) indicate that an intensified regimen is superior to single-agent osimertinib in terms of OS and progression-free survival. Selecting the appropriate combination for an individual patient accordingly requires an informed shared decision-making process, he continued. The clinical benefits of a using a combination regimen must be adequately conveyed to the patient while other factors such as the regimen’s safety profile and administrative convenience must also be considered, he 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.