Adding bevacizumab to cisplatin and pemetrexed improves survival, but at a cost of higher toxicity.
Malignant pleural mesothelioma (MPM) is a challenging disease with few treatment options. In chemo-naive patients, pemetrexed plus a platinum agent remains the standard of care. To determine the potential benefit of adding bevacizumab to this regimen, French investigators conducted a randomized, controlled, open-label, phase III trial in which 448 patients with chemotherapy-naive, unresectable MPM received pemetrexed and cisplatin (PC) or pemetrexed and cisplatin plus bevacizumab (PCB) for 6 cycles; bevacizumab was continued as maintenance therapy in the PCB group….
This is the first randomized study to demonstrate efficacy of a triplet regimen and an anti-angiogenic agent for MPM patients. However, the associated toxicities require close monitoring of patients and limitations in patient eligibility. Moreover, this trial was strict in age eligibility (<76 years), and 97% of patients had performance-status 0–1. In addition, although it is common in the US (despite lack of randomized data) to give maintenance pemetrexed after 4–6 cycles of platinum-pemetrexed, this was not done in the current trial. Thus, it is unknown whether this triplet regimen with bevacizumab would provide a similar survival benefit compared with platinum-pemetrexed plus maintenance pemetrexed. Additional front-line anti-angiogenic trials are under way to assess other combination regimens, including pemetrexed and cisplatin plus cediranib (NCT01064648) and pemetrexed and cisplatin plus nintedanib (NCT01907100).