Dr. Gerard Zalcman
Malignant pleural mesothelioma (MPM) is a locoregional cancer in which VEGF and VEGF receptors are highly expressed. The phase III randomized, open-label IFCT-GFPC-0701 MAPS trial was conducted to determine if the addition of the VEGF-specific angiogenesis inhibitor bevacizumab to standard chemotherapy would affect overall survival (OS) in patients with MPM (Abstract 7500
). Gérard Zalcman, MD, PhD, of Caen University Hospital, France, presented the results of this study during the Lung Cancer—Non–Small Cell Local-Regional/Small Cell/Other Thoracic Cancers Oral Abstract Session held on Saturday, May 30. The study was sponsored by the French Cooperative Thoracic Intergroup and was conducted at 73 centers in France. Key eligibility requirements included being age 18-76, having unresectable histologically proven MPM, having at least one CT-measurable or -evaluable lesion, World Health Organization performance status 0-2, weight loss less than 10% of normal within the previous 3 months, and prior prophylactic radiation therapy. Patients were randomly selected 1:1 to receive 500 mg/m² of intravenous pemetrexed with 75 mg/m2
of cisplatin every 21 days for six cycles or the same regimen with the addition of 15 mg/kg of intravenous bevacizumab. The primary endpoint was OS.
A total of 448 patients were enrolled, with 225 patients receiving standard chemotherapy and 223 patients receiving bevacizumab plus standard chemotherapy. Approximately 75% were men, the median age was 65.7 years (range 34.7-75.9), and an epithelioid histology was present in 80.6% of patients. In the intention-to-treat (ITT) population, the median OS in the bevacizumab arm was 18.82 months (95% CI [15.90, 22.62]) compared with 16.07 months (95% CI [14.00, 17.93]) in the standard chemotherapy arm (stratified hazard ratio [HR] 0.76, 95% CI [0.61, 0.94]; p = 0.0127; Fig. 1). Median progression-free survival was 9.59 months (95% CI [8.49, 10.59]) in the bevacizumab arm compared with 7.48 months (95% CI [6.79, 8.13]) in the standard chemotherapy arm (stratified HR 0.61, 95% CI [0.50, 0.75]; p < 0.0001), also in the ITT population. All subgroup analyses favored the addition of bevacizumab with the exception of poor prognosis.
The safety analysis indicated that significantly more patients who received bevacizumab experienced grade 3/4 events (71.2%) compared with patients who received standard chemotherapy alone (62.1%; p = 0.04). In addition, significantly more grade 3/4 events of hypertension (23.0% vs. 0%; p < 0.0001) and arterial and venous thrombotic events (5.8% vs. 0.9%; p = 0.004) were reported among patients who received bevacizumab. Global quality-of-life measures were similar between the two arms. The overall conclusion was that the addition of bevacizumab to pemetrexed and cisplatin led to longer survival with acceptable toxicity in patients with MPM.
Discussant Anna K. Nowak, MBBS, PhD, FRACP, of the Sir Charles Gairdner Hospital, Australia, congratulated the investigators on conducting a well-designed study. Dr. Nowak noted that whether the bevacizumab, pemetrexed, and cisplatin triplet is widely adopted as a new standard of care in this patient population will depend on several factors, particularly cost-effectiveness and reimbursement decisions made by health care systems in different parts of the world.
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