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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.
Results were as follows:
Median overall survival (OS; the primary outcome) was improved with PCB versus PC (18.8 vs. 16.1 months; P=0.0167), as was median progression-free survival (PFS; 9.2 vs. 7.3 months; P<0.0001).
Poststudy therapy was needed by fewer PCB than PC recipients (62.0% vs. 72.4%).
Fatigue, general condition, and activity levels were improved in PCB recipients, but constipation was improved in PC recipients.
Grade 3–4 adverse events occurred in more PCB recipients (71% vs. 62%), and more PCB recipients experienced grade >3 hypertension (23% vs. 0%), grade >3 arterial/venous thrombotic events (5.8% vs. 0.9%), and hemorrhage of any grade (mostly grade 1–2 epistaxis; 41.0% vs. 7.1%).
More PCB recipients stopped treatment because of adverse effects (24.3% vs. 6.0%; P<0.0001).
Zalcman G et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): Randomised, controlled, open-label, phase 3 trial. Lancet 2015 Dec 21; [e-pub]. (http://dx.doi.org/10.1016/S0140-6736(15)01238-6)
Comment
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).