An interim analysis of the phase II RAMOSE trial reveals that adding ramucirumab to osimertinib significantly extends progression-free survival (PFS) in patients with tyrosine kinase inhibitor (TKI)-naive, EGFR-mutant metastatic non-small cell lung cancer (NSCLC). The study, led by Xiuning Le, MD, PhD, from The University of Texas MD Anderson Cancer Center, was published in the Journal of Clinical Oncology.
Study Design and Patient Population
The open-label, multicenter trial enrolled 139 evaluable patients who were randomly assigned in a 2:1 ratio. Ninety-three patients received ramucirumab at 10 mg/kg every 3 weeks plus osimertinib at 80 mg once daily, while 46 patients received osimertinib at 80 mg once daily. The primary endpoint was progression-free survival.
Baseline characteristics were well balanced between the treatment arms. The patients’ median age was 65 years, 71% were women, and 62% were White. Forty-six percent of patients had stable central nervous system (CNS) metastasis, 69% had exon 19 deletions, 31% had L858R mutations, and 9.4% had received prior chemotherapy.
Significant Improvement in Progression-Free Survival
With a median follow-up of 16.6 months, the median progression-free survival was 24.8 months (95% CI = 17.9 months to not reached) in the combination group compared to 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 one-year PFS rates were 77% and 62%, respectively, and the two-year PFS rates were 51% and 30%, respectively.
"The PFS benefit of osimertinib with ramucirumab was observed across most of the major subgroups, regardless of age, sex, race, types of EGFR mutations, and presence of CNS metastasis," the researchers noted.
The objective response rate was 76.3% in the combination arm and 80.4% in the monotherapy arm (P = .59). The disease control rates were 96.8% and 95.7%, respectively (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).
Safety and Tolerability
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. Adverse events led to treatment discontinuation in 9.7% of the combination group vs 8.7% of the control group.
The most common treatment-related AEs in the combination arm were diarrhea (67.7%), skin rash (60.2%), paronychia (37.6%), epistaxis (35.5%), and fatigue (35.5%). The most common treatment-related AEs in the monotherapy arm were diarrhea (63.0%), skin rash (52.2%), and paronychia (30.4%).
Implications for Clinical Practice
The investigators concluded that "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."
These findings suggest that the combination of ramucirumab and osimertinib represents a promising first-line treatment option for patients with EGFR-mutant NSCLC, offering a significant improvement in progression-free survival compared to osimertinib alone.
