The combination of osimertinib plus chemotherapy led to a median overall survival of 47.5 months compared with 37.6 months with osimertinib monotherapy in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC) who had not received prior treatment for advanced disease, according to final overall survival analyses from the phase III FLAURA2 trial presented at the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract LBA77) and published in The New England Journal of Medicine.
“This is the longest overall survival in this patient population that we've seen in any clinical trial to date. It shows that combination therapies can lead to improvements over a single agent. [These data help] helps establish osimertinib plus chemotherapy as standard-of-care first-line therapy,” stated presenting author and co-principal investigator Pasi A. Jänne, MD, PhD, Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute.
Study Design
The international, open-label phase III FLAURA2 trial included patients (n = 557) with advanced NSCLC and EGFR mutations (exon 19 deletions or L858R mutations) who had not previously received therapy for advanced disease. Patients were randomly assigned 1:1 to receive either osimertinib plus pemetrexed and cisplatin or carboplatin or osimertinib monotherapy. Overall survival was a key secondary endpoint of the study.
Previous results from the study showed that the combination significantly reduced the risk for disease progression or death compared with osimertinib monotherapy (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.49–0.79; P < .001).
Study Findings
The risk for death was reduced by 23% with the addition of chemotherapy to osimertinib vs osimertinib alone as first-line therapy for patients with EGFR-mutated advanced NSCLC (HR = 0.77; 95% CI = 0.61–0.96; P = .02).
Consistent survival benefits from the combination regimen were observed across all prognostic subgroups analyzed, and HRs were consistent with the HR for the overall population. In patients with baseline central nervous system (CNS) metastases, the median overall survival was 40.9 months with the combination vs 29.7 months with the single agent (HR = 0.72), and the median overall survival in patients without CNS metastases was not reached vs 43.9 months, respectively (HR = 0.77).
In patients with L858R mutations, the median overall survival was 38.1 months in the combination arm vs 32.4 months in the single-agent arm (HR = 0.76); in patients with exon 19 deletions, the median overall survival was not reached vs 43.0 months, respectively (HR = 0.76). Patients with TP53 alterations had a median overall survival of 51.1 months with osimertinib and chemotherapy vs 43.1 months with osimertinib alone (HR = 0.71). The median overall survival was not reached in either arm for patients with wild-type TP53 (HR = 0.70).
“This is a very exciting development,” Dr. Jänne said. “These results show the benefits of a combination when started from the very beginning of treatment. I think there's opportunity to use this as a platform to develop additional combination therapies that enhance efficacy from the start of treatment.”
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit nejm.org.
