Gemcitabine with ramucirumab improved overall survival for malignant pleural mesothelioma

1. Compared to the gemcitabine with placebo group, the gemcitabine with ramucirumab group had longer overall survival as a potential second-line treatment for malignant pleural mesothelioma.

2. Commonly experienced treatment-related side effects were neutropenia, hypertension, thromboembolism and fatigue.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Malignant pleural mesothelioma is the most common type of mesothelioma cancer and is often treated with chemotherapy. Currently, platinum compounds with pemetrexed is the first line standard of care treatment. However, there is limited information available on the standard of care as second-line treatment. This study aimed to evaluate the efficacy and safety of gemcitabine with ramucirumab in those with malignant pleural mesothelioma that has progressed during or after the first line standard of care treatment (platinum compounds with pemetrexed). The overall survival rate with the ramucirumab group was higher than the placebo group. There were no treatment related deaths in either group and the most frequent grade 3-4 treatment related side effects reported were neutropenia, hypertension, and fatigue. Thromboembolism was more common in the ramucirumab group. Limitations include the challenges of generalization to different ethnic patient populations, small sample size, and lack of head-to-head comparison with other available second-line treatments. Overall, this study demonstrated that gemcitabine with ramucirumab could be a potential second line treatment for malignant pleural mesothelioma to help improve overall survival.

Click to read the study in The Lancet Oncology

Relevant Reading: Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma

In-Depth [randomized controlled trial]: This was a phase 2, randomized, double-blind, placebo-controlled trial of 165 patients at 26 hospitals in Italy. Eligible patients included those who are age 18 and above, have documented disease progression despite receiving first line chemotherapy (pemetrexed + platinum compound) and have an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2. Patients were excluded if they were taking anticoagulants, had uncontrolled hypertension, and had taken medications that target the VEGF signally pathway. Patients were randomized to receive either gemcitabine with placebo or gemcitabine with ramucirumab. The primary endpoint was the overall survival, starting from the date of randomization to the date of death. 161 patients (81: placebo group, 80: treatment group) were included in the analysis, as per the modified intention-to-treat protocol (patients were included in the analysis if they were placed in the correct randomized group and received their corresponding group’s treatment). The overall survival was longer in the ramucirumab group compared to the placebo group (hazard ratio [HR]: 0.71, 70% confidence interval [CI]: 0.59-0.85; p=0.028) with a longer median overall survival (treatment: 13.8 months, 70% CI: 12.8-14.4; placebo: 7.5 months, 70% CI 6.9-8.9). 44% of the ramucirumab group and 30% in the placebo reported grade 3-4 treatment related side effects. The most frequently reported ones were neutropenia (20% in ramucirumab group vs. 12% in placebo group), hypertension (6% vs. none), and fatigue (5% vs. 4%). Thromboembolism was also reported in 4% of the ramucirumab group versus 2% in the placebo group.

Image: PD

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