Nivolumab with, without ipilimumab benefits patients with malignant pleural mesothelioma
MADRID — Nivolumab alone or in combination with ipilimumab as second- or third-line treatment demonstrated encouraging activity in patients with malignant pleural mesothelioma, according to results of a noncomparative randomized phase 2 trial presented at the European Society for Medical Oncology Congress.
Both the monotherapy and combination regimens achieved their primary endpoints of improved disease control at 12 weeks compared with other treatments.
“These are convincing examples of responses to the activity of immunotherapy drugs in mesothelioma patients and support the National Comprehensive Cancer Network’s decision to recommend this monotherapy or combination therapy as options for second- or third-line therapy in relapsing malignant pleural mesothelioma,” Gerard Zalcman, MD, head of thoracic oncology at Bichat-Claude Bernard Hospital in Paris and past president of the French Cooperative Thoracic Intergroup, said during his presentation.
Malignant pleural mesothelioma is a rare disease typically caused by occupational exposure to asbestos. Standard first-line therapy consists of pemetrexed and platinum chemotherapy, with or without bevacizumab (Avastin, Genentech).
No treatment is recommended for patients who progress, as second-line treatments often demonstrate limited efficacy. Prior studies suggest disease control rates are less than 30% with all drugs evaluated in this setting.
The MAPS2 trial included 125 adults (median age, 71.8 years; range, 32.5-88.1; 80% men) with pleural malignant mesothelioma who relapsed after one or two lines of pemetrexed and platinum chemotherapy.
The analysis included patients aged older than 18 years with histologically proven malignant pleural mesothelioma that relapsed after one or two previous lines, including pemetrexed/platinum doublet. All patients had measurable disease, with performance status 0 or 1.
Researchers randomly assigned half of patients to monotherapy with the PD-L1 inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) administered at 3 mg/kg every 2 weeks. The other half of patients received nivolumab plus ipilimumab (Yervoy, Bristol-Myers Squibb), a CTLA-4 inhibitor, dosed at 1 mg/kg every 6 weeks. Treatment continued until disease progression or unacceptable toxicity.
Disease control rate at 12 weeks served as the primary endpoint.
After median follow-up of 15 months, median OS was 13.6 months with nivolumab monotherapy and had not been reached in the combination therapy group. The prospect that median survival with the combination is longer than 15 months is “exciting,” Zalcman said.
Researchers reported a higher 1-year OS rate (58% vs. 51%), a higher objective response rate (27.8% vs. 18.5%) and longer median PFS (5.6 months vs. 4 months) in the combination group.
“These overall survival and progression-free survival results support a recent decision by the FDA to grant orphan drug status to the combination therapy for mesothelioma,” Zalcman said.
At 12 weeks, the disease control rate — based on the first 108 patients assessed by blinded independent central review (n = 54 in each group) — was higher in the combination therapy group (50% vs. 44.4%). Researchers also reported a higher tumor response rate (51.6% vs. 39.7%) in the combination group at 12 weeks.
Immunohistochemistry analysis of 99 patients showed 41% expressed PD-L1 by immunohistochemistry; however, PD-L1 expression did not predict longer PFS or OS in the overall cohort or in either treatment group individually.
A higher percentage of patients assigned the combination experienced grade 3 toxicities (22.9% vs. 12.7%) or grade 4 toxicities (3.3% vs. 0%). Three treatment-related deaths occurred in the combination group.
A comparable number of patients in the nivolumab monotherapy group and combination group discontinued therapy (23 vs. 22).
“Both nivolumab or nivolumab plus ipilimumab met their endpoint in second- or third-line malignant pleural mesothelioma patients without any unexpected toxicity, leading to meaningful progression-free and overall survivals” Zalcman and colleagues wrote. “These updated results support the efficacy of checkpoint inhibitors in malignant pleural mesothelioma patients, deserving future phase 3 trials.” – by Chuck Gormley
Zalcman G, et al. Abstract LBA58_PR. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.
Disclosures: Bristol-Myers Squibb funded this study. Zalcman reports advisory roles with Bristol-Myers Squibb, Boehringer-Ingelheim, and Merck Sharp and Dohme; grants and personal fees from Bristol-Myers Squibb, Roche, AstraZeneca and Novartis; and compensation for meeting attendance and accommodations from Bristol-Myers Squibb, Roche, AstraZeneca and Pfizer. Please see the abstract for a list of all other researchers’ relevant financial disclosures.