Bevacizumab Improved Survival in Mesothelioma

Adding the angiogenesis inhibitor bevacizumab to standard cisplatin/pemetrexed chemotherapy prolongs survival by more than 2 months among patients with malignant pleural mesothelioma (MPM), according to authors of the randomized multicenter phase III MAPS (Mesothelioma Avastin Cisplatin Pemetrexed Study) clinical trial in France. The findings were presented at the 2015 World Conference on Lung Cancer in Denver, Colorado (abstract ORAL 11.01).

Median overall survival (OS) was 18.8 months among patients in the bevacizumab group vs 16.1 months in the standard chemotherapy group, reported lead study author Arnaud Scherpereel, MD, PhD, clinical director of the Pneumo-Immuno-Allergy Service and professor at the University Hospital of Lille, France.

The study found that bevacizumab was associated with “only a slight, manageable increase in toxicity…making this triplet a new treatment paradigm for MPM patients who are eligible for bevacizumab and not candidates for ‘curative’ surgery,” he said.

“These are very exciting data and I hope it becomes the standard of care,” commented Philip Bonomi, MD, professor of medical oncology at Rush University Medical Center in Chicago, Illinois.

A total of 448 patients were enrolled in the study at 73 cancer centers between 2008 and 2014. Participants were randomly assigned 1:1 to receive standard cisplatin/pemetrexed chemotherapy either with or without bevacizumab (15 mg/kg every 21 days for 6 cycles). Eligibility criteria included unresectable, histologically confirmed MPM, age younger than 76 years, no prior chemotherapy, performance status 0–2, and no thrombosis or bleeding.

The adjusted hazard ratio (HR) for the OS difference between study groups was 0.76 (95% confidence interval [CI], 0.61–0.94; P = .012), Dr. Scherpereel reported. Bevacizumab was also associated with improved progression-free survival (median PFS, 9.6 months vs 7.5 months; adjusted HR, 0.62 [95% CI, 0.50–0.75]; P < .0001).

Grade 3/4 hematological toxicities were similar between the study arms (49.5% in the bevacizumab group vs 47.3%), but bevacizumab was associated with grade 3 proteinuria and hypertension (3.1% and 23%, respectively), neither of which occurred in patients receiving only standard chemotherapy, Dr. Scherpereel noted. Bevacizumab was also associated with more grade 3/4 arterial thrombotic events than standard chemotherapy alone (2.7% vs 0%).

“Bevacizumab did not show a detrimental effect on quality of life, despite its higher specific non-hematological toxicity,” he said.

Pleural mesothelioma can cause chest pain under the rib cage, dyspnea, painful coughing, and unexplained weight loss. Median overall survival with standard platinum/pemetrexed doublet therapy has previously been found not to exceed 13 months, “with virtually no surviving patients at 5 years,” Dr. Scherpereel noted.

Both study groups in the MAPS trial had longer OS times than previous studies, he cautioned. “But this was true for both arms and still, bevacizumab did better,” he said.