Dr Jänne on the FLAURA2 and MARIPOSA Trials of Single-Agent Osimertinib in EGFR-Mutant NSCLC

Pasi A. Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology, director, Belfer Center for Applied Cancer Science, director, Chen-Huang Center for EGFR Mutant Lung Cancers, senior physician, Dana-Farber Cancer Institute, professor of medicine, Harvard Medical School, discusses key trials evaluating the efficacy of single-agent osimertinib (Tagrisso) in patients with metastatic EGFR-mutated non–small cell lung cancer (NSCLC).

The phase 3 FLAURA2 (NCT04035486) and MARIPOSA (NCT04487080) trials were designed to assess whether patients with disease in the first-line metastatic setting would benefit more from treatment with the third-generation EGFR TKI alone vs an intensified combination regimen, Jänne begins.

In the randomized, open-label, multi-center FLAURA2 study, patients received osimertinib and standard platinum-based chemotherapy or chemotherapy alone, Jänne details. The trial's primary end point was progression-free survival (PFS). According to a recent press release, the trial was reported to have met its primary end point. Results from the trial will be officially released in late 2023, Jänne adds.

The multi-arm MARIPOSA trial is assessing the efficacy of osimertinib monotherapy compared with another third-generation small molecule EGFR inhibitor in patients with previously untreated EGFR-mutant NSCLC, Jänne continues. Patients are given either lazertinib plus the EGFR/MET bispecific antibody amivantamab-vmjw (Rybrevant), lazertinib alone, or osimertinib alone, he expands. The trial's primary end point is also PFS. Findings from this trial have not yet been reported, Jänne notes.

Many patients treated with osimertinib or other third-generation inhibitors in this space experience beneficial, durable responses, while others may experience rapid disease progression, Jänne explains, adding that thelatter group of patients may benefit from intensified therapy. Accordingly, it is critical to identify high-risk features that may steer a patient towards a combination therapy over single-agent osimertinib as early as possible, Jänne concludes.