Checkpoint Inhibitors Show Promise in Patients with Mesothelioma

Phoebe Starr

Immunotherapy, Web Exclusives

Chicago, IL—Immunotherapy holds promise as second-line or third-line treatment of patients with malignant pleural mesothelioma, a rare cancer with increasing incidence. Early findings from the ongoing, phase 2 MAPS-2 clinical trial showed that immunotherapy slowed the growth of malignant pleural mesothelioma after relapse, reported lead investigator Arnaud Scherpereel, MD, PhD, Head, Pulmonary and Thoracic Oncology Department, University Hospital of Lille, France, at the 2017 ASCO annual meeting. MAPS-2 is the largest clinical trial to date of immune checkpoint inhibitor therapy in patients with malignant pleural mesothelioma.

At 12 weeks, progression-free survival (PFS) was reported in 44% of patients who received nivolumab (Opdivo) alone and in 50% of patients who received nivolumab plus ipilimumab (Yervoy). The median overall survival (OS) was 10.4 months with single-agent nivolu­mab, and the OS had not yet been reached for nivolumab plus ipilimumab.

Malignant pleural mesothelioma is an aggressive and a relatively uncommon type of cancer associated with asbestos exposure, which currently has no effective treatment options, explained lead investigator Dr Scherpereel. With available treatments, the disease relapses in all patients, and the median life expectancy is 13 to 15 months.

“Our findings suggest that immunotherapy may provide new hope to patients with relapsed mesothelioma. This randomized, phase 2 trial may be enough to support the use of immune checkpoint inhibitors in this setting, but it is too early to conclude whether nivolumab or the combination of nivolumab plus ipilimumab is better,” stated Dr Scherpereel.

MAPS-2 Clinical Trial

The MAPS-2 clinical trial enrolled 125 patients with unresectable malignant pleural mesothelioma that progressed after a maximum of 1 or 2 previous lines of chemotherapy. Patients were randomized in a 1:1 ratio to receive nivolumab or nivolumab plus ipilimumab until disease progression or until unacceptable toxicity for a maximum of 2 years.

The majority of the patients were male, aged approximately 70 years, and had a good performance status.

The primary end point was the disease control rate. In the first 108 evaluable patients, the disease control rate was 44% in the nivolumab arm versus 50% in the nivolumab plus ipilimumab arm. The objective response rate, according to the Response Evaluation Criteria in Solid Tumors was 18% in the nivolumab monotherapy arm compared with 26% in the combination therapy arm.

“As of the data cutoff on March 31, 2017, preliminary progression-free survival was promising,” said Dr Scherpereel. The median PFS was 4 months with nivolumab monotherapy versus 5.6 months with nivolumab plus ipi­limumab. The median OS was 10.4 months with nivolumab monotherapy and was not yet reached with nivolu­mab plus ipilimumab.

“Disease control rate at 12 weeks was meaningfully increased in both arms. Moreover, patients from both arms of the study seem to have prolonged median overall survival than all previous reports in this setting,” he emphasized.

Adverse events were manageable, the majority of which were mild. The most common adverse events were thyroid problems, colon inflammation, and skin rash. Severe adverse events were more common in the combination arm (18%) compared with the nivolumab monotherapy arm (10%).

Mature survival data, biomarker data, and subgroup analysis of the MAPS-2 clinical trial will be presented 1 year after the last patient was accrued.

Several clinical trials of nivolumab and other checkpoint inhibitors for first-line, second-line, or third-line treatment of malignant pleural mesothelioma are underway.

“Mesothelioma cells build a protective tumor microenvironment to shield themselves against the immune system’s attack and even act against antitumor immune response. Therefore, therapies that shift the tumor microenvironment from a state of immune suppression to one of immune activation may hold promise in MPM [malignant pleural mesothelioma],” explained Dr Scherpereel.

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