OSIMERTINIB plus chemotherapy improved overall survival versus monotherapy in EGFR-mutated advanced NSCLC in a Phase III trial.
Overall Survival Benefit with Osimertinib Plus Chemotherapy
In the final analysis of an international Phase III study, first line osimertinib combined with platinum-pemetrexed achieved a median overall survival of 47.5 months compared with 37.6 months for osimertinib alone. The hazard ratio for death was 0.77 with a 95% confidence interval from 0.61 to 0.96 and a P value of 0.02. These data indicate a clinically meaningful survival advantage for the combination over monotherapy in EGFR-mutated advanced NSCLC.
Trial Design and Population
The open label trial randomly assigned 557 untreated patients with EGFR exon 19 deletion or L858R mutation to receive either osimertinib plus pemetrexed with a platinum agent or osimertinib alone. Dosing included osimertinib 80 mg once daily in both groups with pemetrexed at 500 mg per square meter and cisplatin or carboplatin per protocol. Overall survival was a key secondary end point assessed at the planned final analysis.
Safety and Clinical Considerations
Grade 3 or higher adverse events occurred in 70% of patients receiving osimertinib plus chemotherapy compared with 34% receiving monotherapy. Discontinuation of osimertinib due to adverse events was reported in 12% and 7% of patients respectively. The safety profile reflects the added toxicity expected with platinum-pemetrexed. Events were described as reversible which supports feasibility with careful monitoring, supportive care, and proactive dose management. For patients eligible for platinum-pemetrexed, the survival gains observed with osimertinib plus chemotherapy may justify the increased treatment burden in the first line setting.
This survival signal, coupled with reversible toxicity, suggests an important role for combination therapy in suitable candidates, while reinforcing the need for vigilant adverse event management and individualized discussions about goals of care and treatment intensity.
Reference: Jänne PA et al. Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC. New England Journal of Medicine. 2025;DOI:10.1056/NEJMoa2510308.
