In the Italian phase II RAMES trial reported in The Lancet Oncology, Pinto et al found that the addition of ramucirumab to gemcitabine improved overall survival in the second-line treatment of malignant pleural mesothelioma.
As noted by the investigators, “There is a preclinical rationale for inhibiting angiogenesis in mesothelioma. We aimed to assess the efficacy and safety of the anti–VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated malignant pleural mesothelioma.”
In the double-blind multicenter trial, 161 patients who had experienced disease progression during or after first-line pemetrexed/platinum were randomly assigned between December 2016 and July 2018 to receive gemcitabine at 1,000 mg/m² on days 1 and 8 every 3 weeks plus either ramucirumab at 10 mg/kg (n = 80) or placebo (n = 81) on day 1 every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
At database lock (March 2020), median follow-up was 21.9 months (interquartile range = 17.7–28.5 months). Median overall survival was 13.8 months (70% confidence interval = 12.7–14.4 months) in the gemcitabine/ramucirumab group vs 7.5 months (70% CI = 6.9–8.9 months) in the control group (hazard ratio [HR] = 0.71, 70% CI = 0.59–0.85, P = .028); 6- and 12-month rates were 76.0% vs 63.9% and 56.5% vs 33.9%, respectively.
Median progression-free survival was 6.4 months (70% CI = 5.5–7.6 months) in the gemcitabine/ramucirumab group vs 3.3 months (70% CI = 3.0–3.9 months) in the control group (HR = 0.79, 70% CI = 0.66–0.94, P = .082). Objective responses—all partial responses—were observed in 6% vs 10% of patients, with median response durations of 8.4 vs 5.4 months. Disease control rates were 73% vs 52%.
Grade 3 or 4 treatment-related adverse events occurred in 44% of patients in the gemcitabine/ramucirumab group and 30% of the control group; the most common in the combination group were neutropenia (20% vs 12%), hypertension (6% vs 0%), and fatigue (5% vs 4%). Treatment-related serious adverse events occurred in 6% vs 5% of patients, the most commonly reported being thromboembolism (4% vs 2%). No treatment-related deaths were reported.
The investigators concluded, “Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favorable safety profile. This combination could be a new option in this setting.”
Paolo Andrea Zucali, MD, of the Department of Biomedical Sciences, Humanitas University, Milan, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Eli Lilly Italy. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.