In an interim analysis of the phase II RAMOSE trial, reported in the Journal of Clinical Oncology, Le et al found that the addition of ramucirumab to osimertinib significantly prolonged progression-free survival as initial treatment in patients with tyrosine kinase inhibitor (TKI)-naive EGFR-mutant metastatic non–small cell lung cancer (NSCLC).
Study Details
In the U.S. open-label multicenter trial, 139 evaluable patients were randomly assigned 2:1 between October 2019 and July 2023 to receive ramucirumab at 10 mg/kg every 3 weeks plus osimertinib at 80 mg once daily (n = 93) or osimertinib at 80 mg once daily (n = 46). The primary endpoint was progression-free survival.
Progression-Free Survival
At the preplanned interim analysis, median follow-up was 16.6 months. Median progression-free survival was 24.8 months (95% confidence interval [CI] = 17.9 months to not reached) in the combination group vs 15.6 months (95% CI = 11.7–22.8 months) in the control group (hazard ratio = 0.55, 95% CI = 0.32–0.93, P = .026); the rates were 77% vs 62% at 1 year and 51% vs 30% at 2 years, respectively.
The objective response rate was 76.3% vs 80.4% (P = .59), and the disease control rate was 96.8% vs 95.7% (P = .74). Overall survival data were immature at the time of analysis; death had occurred in 11.8% vs 19.6% of patients (P = .221).
Adverse Events
Grade 3 adverse events were observed in 53% of the ramucirumab/osimertinib group vs 41% of the osimertinib group; one grade 4 event (hyponatremia) was observed in the combination group, and no grade 5 events were reported. The most common grade 3 adverse event was hypertension (22.6%) in the combination group, with no other event type occurring in more than three patients. Anemia was reported in more than one patient in the control group. Adverse events led to treatment discontinuation in 9.7% of the combination group vs 8.7% of the control group.
The investigators concluded: “Ramucirumab plus osimertinib significantly prolonged [progression-free survival] compared with osimertinib alone in patients with TKI-naive EGFR-mutant NSCLC. The combination is safe and well tolerated.”
Xiuning Le, MD, PhD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eli Lilly and Company. For full disclosures of the study authors, visit ascopubs.org.
