As reported in The New England Journal of Medicine by Planchard et al, the phase III FLAURA2 trial has shown superior progression-free survival with osimertinib plus platinum-based chemotherapy vs osimertinib alone in the first-line treatment of EGFR-mutant advanced non–small cell lung cancer (NSCLC).
Study Details
In the open-label international trial, 557 patients with exon 19 deletions or L858R mutations who had received no prior treatment for advanced disease were randomly assigned between June 2020 and December 2021 to receive osimertinib at 80 mg once daily with the investigator’s choice of chemotherapy (n = 279) or osimertinib at 80 mg once daily alone. Chemotherapy consisted of pemetrexed at 500 mg/m2 plus either cisplatin at 75 mg/m2 or carboplatin at AUC 5 every 3 weeks for four cycles. Patients in the osimertinib/chemotherapy group also received pemetrexed maintenance.
Overall, 64% of patents in the osimertinib/chemotherapy group and 63% in the osimertinib-alone group were Asian. The primary endpoint was investigator-assessed progression-free survival.
Progression-Free Survival
Median progression-free survival was 25.5 months (95% confidence interval [CI] = 24.7 months to not estimable) in the osimertinib/chemotherapy group vs 16.7 months (95% CI = 14.1–21.3 months) in the osimertinib monotherapy group (hazard ratio [HR] = 0.62, 95% CI = 0.49–0.79, P < .001). The rate at 24 months was 57% vs 41%. Hazard ratios were 0.49 (95% CI = 0.30–0.81) among 140 Chinese patients, 0.76 (95% CI = 0.53–1.09) among 214 non-Chinese Asian patients, and 0.55 (95% CI = 0.37–0.83) among 203 non-Asian patients.
KEY POINTS
- Osimertinib plus chemotherapy significantly improved progression-free survival vs osimertinib alone in patients with EGFR-mutant NSCLC.
- Median progression-free survival was 25.5 months vs 16.7 months.
Among 226 patients with central nervous system (CNS) metastases at baseline, median progression-free survival was 24.9 months vs 13.8 months (HR = 0.47, 95% CI = 0.33–0.66). Among 331 patients without CNS metastases, median progression-free survival was 27.6 months vs 21.0 months (HR = 0.75, 95% CI = 0.55–1.03).
Objective responses were observed in 83% vs 76% of patients. Median response duration was 24.0 months (95% CI = 20.9–27.8 months) vs 15.3 months (95% CI = 12.7–19.4 months).
At data cutoff (27% data maturity for overall survival), death had occurred in 71 patients in the osimertinib/chemotherapy group vs 78 in the osimertinib monotherapy group (HR = 0.90, 95% CI = 0.65–1.24, P = .52). Overall survival rates were 89% vs 92% at 12 months and 79% vs 73% at 24 months.
Adverse Events
Grade ≥ 3 adverse events occurred in 64% of the osimertinib/chemotherapy group vs 27% of the osimertinib monotherapy group (no grade 4 events). Most adverse events in the osimertinib/chemotherapy group were hematologic, including anemia (20%) and neutropenia (14%).
Serious adverse events occurred in 38% vs 19% of patients. Adverse events led to discontinuation of osimertinib in 11% of the osimertinib/chemotherapy group and in 6% of the osimertinib monotherapy group. Fatal adverse events considered possibly related to study treatment were reported in five patients in the osimertinib/chemotherapy group and one patient in the osimertinib group.
The investigators concluded: “First-line treatment with osimertinib/chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC.”
David Planchard, MD, PhD, of Institut Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Villejuif, France, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit nejm.org.
