A combination of osimertinib and ramucirumab has shown promising results in patients with tyrosine kinase inhibitor (TKI)-naïve epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). The multicenter, randomized phase II RAMOSE trial demonstrated a significant improvement in progression-free survival (PFS) compared to osimertinib alone.
The study, involving 159 patients with locally advanced or metastatic EGFR-mutant NSCLC across 11 centers in the United States, compared the efficacy of ramucirumab plus osimertinib against osimertinib monotherapy. Patients were randomized in a 2:1 ratio to receive either the combination therapy or osimertinib alone. The primary endpoint was PFS, with secondary outcomes including objective response rate (ORR) and safety and tolerability.
Progression-Free Survival Improvement
The median PFS was 24.8 months in patients receiving ramucirumab plus osimertinib, compared to 15.6 months in those receiving osimertinib monotherapy (hazard ratio, 0.55; 95% CI, 0.32 to 0.93; log-rank P = .023). This clinically significant improvement suggests that the addition of ramucirumab to osimertinib provides a substantial benefit in delaying disease progression.
Objective Response and Safety
While the PFS was significantly improved, the objective response rate (ORR) was similar in both groups: 76.3% (95% CI, 67.7 to 85.0) for the combination therapy and 80.4% (95% CI, 69.0 to 91.9) for osimertinib monotherapy (P = .59). The disease control rate (DCR) also showed no significant difference between the two groups. Regarding safety, the rates of adverse event (AE)-related discontinuation were comparable, with 9.7% in the combination arm and 8.7% in the osimertinib monotherapy arm.
Implications for Treatment
These findings suggest that the combination of ramucirumab and osimertinib could be a valuable treatment option for patients with EGFR-mutant NSCLC who are TKI-naïve. The study supports further investigation into the potential of VEGF pathway inhibition in combination with EGFR TKIs in this patient population. The current standard of care typically involves third-generation EGFR TKIs like osimertinib, either alone or with platinum-based chemotherapy. The RAMOSE trial introduces a potential new avenue for treatment, especially considering emerging evidence suggesting the susceptibility of EGFR-mutant NSCLC to VEGF pathway inhibition.
Study Details
The study included patients aged 18 years or older with locally advanced or metastatic NSCLC, documented EGFR mutation, and no prior TKI exposure. The median age of participants was 65 years (range, 37-83), and 71.2% were female. After a median follow-up of 16.6 months, the results indicated a clear benefit in PFS with the combination therapy. Ramucirumab is a monoclonal antibody targeting VEGFR2, and its combination with erlotinib, a first-generation TKI, is already approved for EGFR-mutant NSCLC. However, this trial is among the first to investigate the combination of ramucirumab with a third-generation TKI.
