Osimertinib Plus Chemotherapy Significantly Extends Survival in Advanced EGFRm NSCLC

Final overall survival (OS) data from the FLAURA2 phase 3 trial (NCT04035442) demonstrate that osimertinib (Tagrisso) combined with platinum-based chemotherapy significantly improves OS for patients with previously untreated, locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non–small cell lung cancer (NSCLC). These findings reinforce the combination's potential as a new standard of care, building upon its previously reported progression-free survival (PFS) benefits.¹

The FLAURA2 trial, a randomized, open-label, multicenter, global, phase 3 study, compared osimertinib monotherapy with osimertinib plus chemotherapy (pemetrexed and cisplatin or carboplatin) in 557 patients. The final OS analysis, a key secondary end point, showed a statistically significant and clinically meaningful improvement with the combination therapy. This sustained survival benefit aligns with prior interim OS results and the previously established longest median PFS reported in this setting. Full data will be presented at an upcoming medical meeting.

“When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in [the first] line, where treatment duration can be long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with [first]-line advanced EGFR-mutated lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression,” said Pasi A. Jänne, MD, PhD, senior vice president for translational medicine and thoracic medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, in a press release.

Osimertinib, a third-generation, irreversible EGFR-tyrosine kinase inhibitor (TKI), has demonstrated clinical activity across various stages of EGFRm NSCLC, including efficacy against central nervous system metastases. The rationale behind combining osimertinib with chemotherapy is to address mechanisms of resistance and disease progression that can occur with TKI monotherapy, thereby offering a more durable response.

The safety profile of osimertinib plus chemotherapy remained manageable with longer follow-up, consistent with the known profiles of the individual agents. While adverse event rates were higher in the combination arm, these were predominantly well-characterized chemotherapy-related toxicities. Discontinuation rates due to adverse events and on-target toxicities were low in both treatment arms, indicating a tolerable safety profile for the combination regimen.

Lung cancer remains a leading cause of cancer-related mortality globally, with NSCLC accounting for the majority of cases. Approximately 10% to 15% of patients with NSCLC in populations and 30% to 40% in Asia present with EGFRm NSCLC. Despite significant advancements with EGFR TKIs in the first-line setting, the development of resistance mechanisms and subsequent disease progression represent a substantial unmet medical need. The FLAURA2 findings address this need by providing a more potent initial treatment strategy that can extend survival.

In February 2024, the FDA approved the osimertinib-chemotherapy combination in this intent-to-treat population, supported by findings from FLAURA2.²

REFERENCES:

1. Tagrisso plus chemotherapy demonstrated statistically significant and clinically meaningful improvement in overall survival in EGFR-mutated advanced lung cancer. News release. AstraZeneca. July 21, 2025. Accessed July 21, 2025. https://tinyurl.com/2s5ptsa5

2. FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer. News release. FDA. February 16, 2024. Accessed July 21, 2025. http://tinyurl.com/2s4jxkr4