Bevacizumab for Newly Diagnosed Malignant Pleural Mesothelioma

Summary and Comment |
January 21, 2016

Bevacizumab for Newly Diagnosed Malignant Pleural Mesothelioma

  1. Anne S. Tsao, MD

Adding bevacizumab to cisplatin and pemetrexed improves survival, but at a cost of higher toxicity.

  1. Anne S. Tsao, MD

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).

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).

Editor Disclosures at Time of Publication

  • Disclosures for Anne S. Tsao, MD at time of publication Consultant / Advisory board Genetech; Roche; Medimmune; Novartis; Astellas; Boehringer-Ingelheim; Eli Lilly Speaker’s bureau Genetech; Roche; Medimmune; Novartis; Astellas; Boehringer-Ingelheim; Eli Lilly Grant / Research support Department of Defense; SWOG Leadership positions in professional societies American Medical Association (Member); American Association of Cancer Research (Member); American Society of Clinical Oncology (Member); AACR-Women in Cancer Research (Member); International Mesothelioma Interest Group (Member); SWOG (Member); International Association for the Study of Lung Cancer (Communications Committee Chair); American Radium Society (Chair); RTOG (Member)

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