Ipilimumab, nivolumab shows promising control of mesothelioma

The combination of nivolumab and ipilimumab showed a promising rate of 12-week disease control among patients with recurrent malignant pleural mesothelioma, according to interim results of a phase 2 study presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.

The combination also led to mild toxicity.

Researchers have been interested to evaluate the role of immunotherapy in mesothelioma. In a previous study, Paul Baas, MD, PhD, professor in the department of thoracic oncology at The Netherlands Cancer Institute, and colleagues showed nivolumab (Opdivo, Bristol-Myers Squibb) conferred a 50% 12-week disease control rate among patients with recurrent mesothelioma.

“We reported the same study last year, but with nivolumab alone,” Baas said during his presentation. “It was more than logical to expand it to evaluate the addition of ipilimumab in this patient cohort.”

In the current analysis, Baas and colleagues evaluated the combination of 240 mg nivolumab once every 2 weeks and 1 m/kg ipilimumab (Yervoy, Bristol-Myers Squibb) weeks 1, 7, 13 and 19 for 38 patients (median age, 65 years; men, n = 30) with recurrent mesothelioma. Patients had a performance status of 0 to 1 and pleural lesions available for biopsy before and 6 weeks after treatment.

Patients underwent CT scans every 6 weeks for analysis and duration of response.

Disease control rate at 12 weeks served as the study’s primary endpoint.

Three patients did not commence therapy due to disease progression or inability to undergo biopsy. Another two patients stopped after the first cycle due to progression and withdrawn consent.

Twenty-nine patients had paired biopsies, and 27 patients were evaluable for response.

Twenty patients (74%) demonstrated disease control at 12 weeks. This included seven patients (27%) with partial response and 13 patients (48%) with stable disease.

PFS was 144 days, and 15 patients remained on treatment.

Grade 2 infusion reaction occurred in 13 patients. Researchers also reported pleural effusion and dyspnea in four patients each (grade 2, n =2; grade 3-4, n = 2 for each). Four patients experienced serious adverse events; these included diarrhea, dyspnea, pleural effusion and delirium.

All observed toxicity was well managed, Baas said.

“The combination of nivolumab and ipilimumab shows a very good disease control rate, even though we have only reported on the first three-quarters of patients enrolled,” Baas said.

“At this moment, immunotherapy treatment has changed the current practice and should be offered in the second line or even the first line to patients with mesothelioma,” Baas added. “We need additional translational research to identify patients who are really benefiting from treatment, and those for whom this treatment would only be a waste of time.” – by Alexandra Todak

Reference:

Baas P, et al. Abstract OA 02.02. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Oct. 15-18, 2017; Yokohama, Japan.

Disclosures: Baas reports consultant/advisory roles with Aduro, Bayer, Bristol-Myers Squibb, Genentech, Merck and Verastem, and research support from Bristol-Myers Squibb and Merck. Please see the abstract for a list of all other authors’ relevant financial disclosures.