Second-line gemcitabine plus ramucirumab significantly improves overall survival

To date, second-line chemotherapy is not the standard of care in patients with malignant pleural mesothelioma (MPM). The multicenter, double-blind, randomised 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 RAMES study enrolled 161 patients with progressive disease after first-line treatment with platinum/pemetrexed. Patients were randomised to gemcitabine (1,000 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. The primary endpoint of the trial was overall survival (OS). Secondary endpoints were progression-free survival (PFS), response rate, safety, and quality of life.

“Addition of ramucirumab to gemcitabine significantly improved median OS”, reported Maria Pagano (General Hospital Arcispedale Santa Maria Nuova, Italy) [1]. “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 72.5% (0%, 6.3%, 66.3%) in the gemcitabine/ramucirumab arm and 51.9% (0%, 9.9%, 42.0%) 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.

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   1. Pagano M, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 9004.

Posted on 8 September 202018 March 2024