(Barcelona, Spain September 7, 2025, 10:45 a.m. CEST / UTC +2) Final overall survival (OS) results from the Phase III FLAURA2 trial demonstrate that first-line osimertinib plus chemotherapy significantly improves OS compared to osimertinib monotherapy in patients with EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC).
These findings, presented today at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer, support osimertinib plus chemotherapy as a new standard-of-care treatment option in this patient population, according to David Planchard, MD, PhD, Department of Medical Oncology, Institut Gustave Roussy, Thoracic Unit.
Osimertinib, a third-generation, CNS-active EGFR tyrosine kinase inhibitor (EGFR-TKI), is currently a preferred first-line treatment for EGFRm advanced NSCLC. The global, open-label, randomized Phase III FLAURA2 study (NCT04035486) evaluated whether adding chemotherapy (pemetrexed with cisplatin or carboplatin) to osimertinib could provide additional survival benefit.
A total of 557 patients with previously untreated, EGFRm (Ex19del/L858R) locally advanced or metastatic NSCLC were randomized 1:1 to receive osimertinib plus chemotherapy (n=279) or osimertinib monotherapy (n=278). The primary endpoint was progression-free survival (PFS), with OS as a key secondary endpoint. Patients were eligible if they had a WHO performance status of 0 or 1, and stable CNS metastases were permitted.
At a median follow-up of approximately 57% maturity, osimertinib plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS versus osimertinib monotherapy (HR 0.77; 95% CI 0.61–0.96; p=0.02). Median OS was 47.5 months with combination therapy versus 37.6 months with monotherapy. The 36-month survival rate was 63% versus 51%, respectively. The OS benefit was consistent across predefined subgroups.
The safety profile of the combination was manageable and consistent with the known profiles of the individual treatments. No new safety signals emerged with longer follow-up. Adverse events (AEs) leading to discontinuation of osimertinib occurred in 12% of patients in the combination arm versus 7% in the monotherapy arm.
"These compelling overall survival results confirm osimertinib plus chemotherapy as a first-line standard of care for patients with EGFR-mutated advanced NSCLC," said Dr. Planchard. "By combining osimertinib with chemotherapy, we are able to extend survival for these patients while maintaining a manageable safety profile."
The FLAURA2 trial results reinforce osimertinib as the backbone therapy in this setting, with the addition of chemotherapy offering a meaningful OS advantage for patients with EGFRm advanced NSCLC, he said.
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