A new phase 3 clinical trial has found that combining osimertinib with platinum–pemetrexed chemotherapy significantly improves overall survival in patients with newly diagnosed EGFR-mutated advanced non-small cell lung cancer (NSCLC) compared to osimertinib alone.

The findings from the global FLAURA2 study, co-led by researchers at the Dana-Farber Cancer Institute and Gustave Roussy (Grand Paris, Villejuif, France), were presented at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin and published simultaneously in the New England Journal of Medicine.

Combination Therapy Extends Survival to Nearly 4 Years

According to the trial results, patients treated with osimertinib plus platinum–pemetrexed achieved a median overall survival of 47.5 months, compared with 37.6 months for those who received osimertinib monotherapy.

“This is the longest overall survival seen in this patient population in any clinical trial to date,” said Dr. Pasi A. Jänne, co-principal investigator of the study and director of the Lowe Center for Thoracic Oncology at Dana-Farber.
“It shows that combination therapies can lead to meaningful improvements over a single agent and helps establish osimertinib plus chemotherapy as a new standard of care for first-line treatment.”

Benefits Observed in High-Risk Patient Groups

The study also revealed that the combination therapy provided substantial benefit for patients with central nervous system (CNS) metastases — a group typically associated with poorer outcomes.
Median overall survival for these patients was 40.9 months in the combination group versus 29.7 months for those on osimertinib alone.

Between 10–15% of NSCLC patients in the U.S. and up to 50% in Asia harbor epidermal growth factor receptor (EGFR) mutations, which drive tumor growth.
The FLAURA2 trial investigated whether adding platinum–pemetrexed chemotherapy upfront could prevent early recurrence seen in patients receiving osimertinib monotherapy.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), was already known to extend progression-free survival, but this new data confirms that adding chemotherapy provides a clinically meaningful overall survival advantage.

FDA Approval and Clinical Implications

The U.S. Food and Drug Administration (FDA) approved the combination of osimertinib and chemotherapy in February 2024 based on earlier FLAURA2 data demonstrating improved progression-free survival.
This latest analysis — showing a nearly 10-month survival advantage — further strengthens the case for adopting the combination as a standard first-line therapy.

“This is a very exciting development,” said Dr. Jänne. “These results show the benefit of starting combination therapy early and open the door to developing even more effective treatment strategies for EGFR-mutant lung cancer.”

Side Effects and Patient Considerations

As expected, patients receiving combination therapy experienced more chemotherapy-related side effects, including nausea, vomiting, fatigue, and bone marrow suppression.
However, researchers noted that these effects were most pronounced during the initial treatment phase and tended to lessen during maintenance therapy with osimertinib and pemetrexed.

“There are now multiple options for patients with newly diagnosed EGFR-mutant NSCLC, including both combination and single-agent therapies,” Jänne added.
“Shared decision-making between clinicians and patients will be essential to balance the survival benefit against potential side effects.”

Source: Dana-Farber Cancer Institute – “Osimertinib plus chemotherapy improves survival in EGFR-mutated lung cancer”