Bevacizumab Triplet Improves Survival in Mesothelioma

Arnaud Scherpereel,

MD, PhD

Adding bevacizumab (Avastin) to a standard chemotherapy doublet reduced the risk of death by 24% and disease progression by 39% in patients with malignant pleural mesothelioma (MPM), according to results from the phase II/III MAPS trial presented at the 2015 World Conference on Lung Cancer.¹

“The treatment of pemetrexed, cisplatin, and bevacizumab is a new treatment paradigm for patients with malignant pleural mesothelioma,” lead author Arnaud Scherpereel, MD, PhD, head of the Pulmonary and Thoracic Oncology Department and professor at the University Hospital (CHU) of Lille, France, said in a press conference at the World Lung meeting.

The French Cooperative Thoracic Intergroup (IFCT) phase II/III IFCT-GFPC-0701 MAPS trial included 448 chemotherapy-naïve patients enrolled across 73 locations between February 2008 and January 2014. Patients had to have unresectable, histologically confirmed MPM and an ECOG performance status (PS) of 0 to 2 (96.7% had a PS of 0-1). The median patient age was 65.7 years (range, 34.7-75.9).

Patients with brain metastases, thrombosis, or bleeding were not eligible. All patients were required to receive prophylactic radiotherapy (3 x 7 Gy) prior to initiation of chemotherapy and within 28 days of pleural biopsy. Patients were stratified by treatment location, PS (0-1 vs 2), histology (epithelioid vs sarcomatoid/mixed), and smoking status.

MAPS randomized patients in a 1:1 ratio to pemetrexed (500 mg/m2) plus cisplatin (75 mg/m²) either alone (n = 225) or with 15 mg/kg of bevacizumab (n = 223). All treatments were administered on day 1 of a 21-day cycle for 6 cycles. Following 6 cycles, patients in the experimental arm with disease control continued on maintenance bevacizumab at the same dose and schedule until disease progression or unacceptable toxicity. Crossover between arms was not allowed.

Approximately three-fourths of patients in each arm completed all 6 initial treatment cycles. The median number of treatment cycles was 6 in the control arm and 9 in the bevacizumab arm.

Response was assessed with CT-scans every 3 cycles in both arms using modified RECIST criteria for mesothelioma. The primary phase III endpoint for MAPS was overall survival (OS) and secondary outcome measures included progression-free survival (PFS) and quality of life.

At a median follow-up of 39.4 months (range, 11.0-83.05), OS was 18.82 months (95% CI, 15.90-22.62) in the bevacizumab arm versus 16.07 months (95% CI, 14.00-17.93) with chemotherapy alone (HR, 0.76; 95% CI, 0.61-0.94; P = .0127). In previous research, median OS with the pemetrexed/cisplatin doublet has been <13 months in patients with MPM, noted Scherpereel. The OS benefit held up across patient subgroups.

Median PFS was 9.59 months with bevacizumab (95% CI, 8.49-10.59) versus 7.48 months (95% CI, 6.79-8.13) in the control arm (HR, 0.61; 95% CI, 0.50-0.75; P <.0001). The best reported median PFS in previously published results with pemetrexed/cisplatin in patients with MPM was about 6 to 7 months, according to Scherpereel.

Data from the MAPS trial were also presented in June at the 2015 ASCO Annual Meeting.² These data showed that rates of grade 3/4 toxicities were slightly higher with bevacizumab at 71.2%, compared with 62.1% in the control arm.

Incidence of hematologic toxicities was similar between arms; however, anemia occurred more frequently in the control arm at 83.5% versus 73.4%. Grade 3/4 anemia occurred in 13.4% and 7.2% of the control and bevacizumab arms, respectively.

Nonhematologic malignancies were also for the most part similar between the treatment arms. However, the bevacizumab arm had higher grade 3/4 rates of hypertension (23.0% vs 0), venous and arterial thromboembolic events (5.8% vs 0.9%), creatinin increase (3.6% vs 1.8%), and hemorrhage (0.9% vs 0).

“Quality of life was preserved in both arms and bevacizumab did not show a detrimental effect on quality of life, despite the higher toxicity,” said lead investigator Gérard Zalcman, MD, president of the IFCT, when presenting the MAPS results at ASCO.

Zalcman added that the bevacizumab triplet regimen is a “new treatment paradigm for pleural mesothelioma patients eligible for bevacizumab who are not eligible for ‘curative’ surgery.”

1. Scherpereel A, Mazières J, Margery J, et al. Bevacizumab 15mg/kg plus cisplatin-pemetrexed (CP) vs CP in malignant pleural mesothelioma (MPM): IFCT-GFPC-0701 MAPS randomized phase 3 trial (ID 2142). Presented at: 16th World Conference on Lung Cancer; September 6-9; Denver, CO. Abstract 2142.
2. Zalcman G, Mazières J, Margery J, et al. Bevacizumab 15mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in malignant pleural mesothelioma (MPM): results of the IFCT-GFPC-0701 MAPS randomized phase 3 trial. J Clin Oncol 33, 2015 (suppl; abstr 7500).

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