To date, second-line chemotherapy is not the standard of care in patients with malignant pleural mesothelioma (MPM). The multicenter, double-blind, randomized phase 2 RAMES Study explored the efficacy and the safety of the addition of the antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2/KDR) ramucirumab to gemcitabine as the second-line treatment in MPM patients after platinum/pemetrexed regimens. The primary endpoint of the trial was overall survival (OS). Second endpoints are progression-free survival (PFS), response rate, safety and quality of life.
The RAMES Study enrolled 161 patients with progressive disease after first-line treatment with platinum/pemetrexed. Patients were randomized to gemcitabine (1000 mg/m2 IV on days 1 and 8 every 21 days) plus placebo or gemcitabine plus ramucirumab (10 mg/kg IV on day 1, of a 21-day cycle), until tolerability or progressive disease. Median number of courses was 3.50 in the gemcitabine/placebo arm and 7.50 in the gemcitabine/ramucirumab arm.
“Addition of ramucirumab to gemcitabine significantly improved median OS”, reported Maria Pagano, oncologist at General Hospital Arcispedale Santa Maria Nuova, Reggio Emilia, Italy, at the virtual meeting of the American Society of Clinical Oncology. “Median OS in the gemcitabine/ramucirumab arm was 13.8 months and 7.5 months in the gemcitabine/placebo arm. OS at 6 and 12 months were 74.7% and 56.5% in the gemcitabine/ramucirumab arm and 63.9% and 33.9% in the gemcitabine/placebo arm, respectively. The beneficial effect of ramucirumab was observed regardless of age, tumor histological type and time-to-progression from the first-line treatment.”
A key secondary endpoint was PFS, which was 6.2 months in the gemcitabine/ramucirumab arm and 3.3 months in the gemcitabine/placebo arm (P=0.26) and disease control rates (complete response, partial response, stable disease, respectively) were 72.50% (0%, 6.25%. 66.25%) in the gemcitabine/ramucirumab arm and 42% (0%, 9.88%, 41.98%) in the gemcitabine/placebo arm. Addition of ramucirumab to gemcitabine did not result in an increase of toxicity. The safety profile was comparable to other anti-angiogenic agents, particularly featuring hypertension and thrombosis.
“The RAMES Study demonstrates that ramucirumab plus gemcitabine can be considered a new option for the second-line treatment in patients with MPM”, concluded Dr. Pagano.
Pagano M, et al. ASCO 2020 virtual meeting, abstract 9004