Bevacizumab With Chemotherapy Doublet Improves Survival for Patients With Mesothelioma

Arnaud Scherpereel, MD, PhD

By adding bevacizumab (Avastin) to a standard chemotherapy doublet, the risk of death is reduced by 24%, with the risk of disease reducing by 39%, in patients who have malignant pleural mesothelioma (MPM), according to results from the phase II/III MAPS trial that was presented at this year’s World Conference on Lung Cancer.¹

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

The French Cooperative Thoracic Intergroup (IFCT) phase II/III IFCT-GFPC-0701 MAPS trial consisted of 448 chemotherapy-naïve patients enrolled across 73 locations between February 2008 and January 2014. Patients were required 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 not eligible were those with brain metastases, thrombosis, or bleeding. 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.

Patients were randomized 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 of the initial treatment cycles. The median number of treatment cycles was 6 for the control arm and 9 for 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), while the 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 who have 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, says Scherpereel.

Data from the MAPS trial were also presented in June at the 2015 ASCO Annual Meeting.²These 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 quite 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).

&ldquo;Quality of life was preserved in both arms and bevacizumab did not show a detrimental effect on quality of life, despite the higher toxicity,&rdquo; said lead investigator G&eacute;rard Zalcman, MD, president of the IFCT, when presenting the MAPS results at ASCO.

Zalcman added that the bevacizumab triplet regimen is a &ldquo;new treatment paradigm for pleural mesothelioma patients eligible for bevacizumab who are not eligible for &lsquo;curative&rsquo; surgery.&rdquo;

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1. Scherpereel A, Mazi&egrave;res 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, Mazi&egrave;res 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 Oncol33, 2015 (suppl; abstr 7500).