A combination of the targeted therapy drug osimertinib with standard chemotherapy extends life by nearly 10 months for patients with a common form of advanced non-small cell lung cancer, according to final results from a landmark clinical trial. The findings show that adding platinum-pemetrexed chemotherapy to the current standard-of-care treatment significantly improves overall survival, establishing a new benchmark for first-line therapy in this patient population.
The global Phase 3 study, known as FLAURA2, provides definitive evidence that the combination approach is superior to using osimertinib alone for patients with locally advanced or metastatic non-small cell lung cancer driven by mutations in the epidermal growth factor receptor (EGFR). These results, which were consistent across various patient subgroups, including those with a poor prognosis, have already begun to change clinical practice since the U.S. Food and Drug Administration approved the regimen earlier in the year based on earlier positive data. The final overall survival data were presented at the European Society for Medical Oncology Congress and the IASLC World Conference on Lung Cancer in 2025.
Details of the FLAURA2 Investigation
The FLAURA2 trial was a global, randomized, open-label Phase 3 study designed to evaluate the efficacy and safety of adding chemotherapy to a targeted therapy backbone. Researchers enrolled 557 patients with previously untreated, EGFR-mutated advanced non-small cell lung cancer. The specific mutations included the most common types: exon 19 deletion (Ex19del) or the exon 21 L858R mutation. Patients with stable central nervous system metastases, a common complication of this cancer, were permitted to enroll in the study, making the trial population representative of real-world patients.
Participants were randomly assigned in a 1-to-1 ratio to one of two treatment groups. The experimental group (279 patients) received 80 mg of oral osimertinib daily plus intravenous pemetrexed and either cisplatin or carboplatin chemotherapy every three weeks for four cycles, followed by maintenance therapy with osimertinib and pemetrexed. The control group (278 patients) received the current standard of care: 80 mg of oral osimertinib daily as a monotherapy. Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) that is highly effective against the cancer-driving mutations and is able to penetrate the central nervous system.
Primary and Secondary Measures of Success
The primary endpoint of the trial was progression-free survival (PFS), which measures how long patients live without their disease worsening. A key secondary endpoint was overall survival (OS), considered the gold standard in oncology trials, which measures how long patients live in total. Researchers followed the participants for a median of over 50 months to gather mature and robust data on the long-term outcomes of the treatment regimens.
A New Benchmark in Patient Survival
The final analysis of the FLAURA2 study demonstrated a statistically significant and clinically meaningful improvement in both overall and progression-free survival for patients receiving the combination therapy. The results exceeded expectations and set a new record for survival in this specific cancer type. Investigators stated that the findings confirm the combination as a new first-line standard of care.
Overall Survival Gains
Patients in the osimertinib-plus-chemotherapy arm achieved a median overall survival of 47.5 months, compared to 37.6 months for those receiving osimertinib alone. This nearly 10-month advantage translates to a 23% reduction in the risk of death (Hazard Ratio [HR] of 0.77). The survival benefit was sustained over time, with the 36-month survival rate being 63% for the combination group versus 51% for the monotherapy group. At the 48-month mark, 49% of combination patients were still alive, compared to 41% of monotherapy patients. Dr. Pasi A. Jänne, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and a co-principal investigator, noted this is the longest overall survival seen in any clinical trial for this patient population to date.
Progression-Free Survival Advantage
The overall survival results build upon the trial’s initial primary endpoint success. The study had previously reported that the combination therapy significantly extended the time before the cancer progressed. Median progression-free survival was 25.5 months for the combination arm, a substantial improvement over the 16.7 months observed in the osimertinib monotherapy arm. This represented a 38% reduction in the risk of disease progression or death, providing the initial powerful evidence that led to regulatory review and approval.
Efficacy in Difficult-to-Treat Subgroups
A crucial finding from the FLAURA2 trial was that the survival benefit of the combination therapy was consistent across nearly all predefined patient subgroups. This included patients often considered to have a poorer prognosis. The exploratory analysis confirmed that adding chemotherapy provided an advantage regardless of baseline risk factors, reinforcing the robustness of the results.
The combination showed a clear overall survival benefit for patients with central nervous system (CNS) metastases at the start of the trial, a group that is notoriously difficult to treat. Similarly, positive outcomes were observed in patients with metastases to the bone or liver. The regimen was also effective regardless of the specific type of EGFR mutation, benefiting patients with either the exon 19 deletion or the L858R mutation. For example, in patients with the L858R mutation, median overall survival was 38.1 months with the combination compared to 32.4 months with monotherapy.
Clinical Impact and Regulatory Standing
The compelling results from FLAURA2 have solidified a new therapeutic strategy for newly diagnosed EGFR-mutant advanced lung cancer. Based on the powerful progression-free survival data, the U.S. Food and Drug Administration (FDA) approved the combination of osimertinib with platinum-based chemotherapy in February 2024 for patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations.
Leading oncologists involved in the study have endorsed the regimen as a new standard of care. Dr. David Planchard of the Institut Gustave Roussy, another co-principal investigator, stated that the compelling overall survival results confirm the combination’s role and that by adding chemotherapy, “we are able to extend survival for these patients while maintaining a manageable safety profile.” The findings reinforce osimertinib as the essential backbone therapy in this setting, with chemotherapy providing a significant and meaningful survival advantage.
Managing the Treatment Safety Profile
While adding chemotherapy to targeted therapy increases toxicity, the safety profile of the combination regimen in the FLAURA2 trial was manageable and consistent with the known individual profiles of the drugs. No new or unexpected safety concerns emerged during the extended follow-up period.
Adverse events were more common in the combination arm, as expected. Side effects leading to the discontinuation of osimertinib occurred in 12% of patients receiving the combination treatment, compared to 7% in the monotherapy arm. Common grade 3 or higher adverse events related to chemotherapy, such as anemia and neutropenia, were observed but were managed with standard supportive care. The overall conclusion from the investigators was that the added benefit in survival far outweighed the manageable increase in side effects for this patient population.
