Nivolumab Alone or With Ipilimumab Controls Disease, Extends Survival, in Mesothelioma

Arnaud Scherpereel, MD, PhD

Nivolumab as monotherapy or in combination with ipilimumab may present a new second- or third-line treatment option for patients with malignant pleural mesothelioma (MPM), based on preliminary findings from a phase II trial where nivolumab alone or in the combination improved disease control and prolonged survival in patients with this rare but aggressive cancer.

Although these results from the MAPS-2 trial suggest a role for immune checkpoint inhibitors in this setting, it’s too early to tell whether nivolumab is better alone or in combination with ipilimumab, explained lead study author Arnaud Scherpereel, MD, PhD, who presented the findings at a presscast at the 2017 ASCO Annual Meeting June 5.

“Both the Nivo-alone arm and the Ipi + Nivo arm reached their first endpoint of meaningful disease control in second- and third-line patients,” said Scherpereel, head of the Pulmonary and Thoracic Oncology Department at the University Hospital (CHU) in Lille, France. “Moreover, patients from both arms of this study seem to have prolonged median overall survival compared to all previous reports in this setting.”

Currently, no treatment has been validated for patients whose MPM progresses after first-line treatment with pemetrexed and a platinum chemotherapy. The disease control rate in the second-line setting is less than 30%, with a median overall survival (OS) of less than 6 to 9 months, Scherpereel reported. Although MPM is relatively rare, “Because of its links to asbestos, we could see an increase in incidence due to the wide use of asbestos in many countries.”

The multicenter MAPS-2 randomized trial represents the largest clinical trial of immune checkpoint inhibitors in mesothelioma to date, its authors noted. The trial enrolled 125 patients from 21 centers between March and August 2016 who had unresectable MPM that progressed after a maximum of 1 or 2 lines of therapy that included a pemetrexed-platinum doublet. Patients had an ECOG performance status of 0 or 1, were a median age of 71.8 years (range, 32.5 to 88.1), and 80% were male.

Patients were evenly randomized to 2 groups which were assessed independently in this noncomparative trial: 1 group received nivolumab (3 mg/kg IV every 2 weeks) as monotherapy, and for the other group, ipilimumab (1 mg/kg every 6 weeks) was added to the nivolumab regimen. Therapy continued until progression or unacceptable toxicity for a maximum of 2 years, and patients were assessed by CT scan every 12 weeks. Scherpereel reported that overall compliance with both regimens was good, with ≥70% of patients having 6 cycles of therapy.

Disease control rate (DCR) at 12 weeks was the study’s primary endpoint. The results Scherpereel reported at ASCO are from the first 108 eligible patients on the study. DCR was 44% for those who received nivolumab alone and 50% among those who received it in combination with ipilimumab. Tumor shrinkage was seen in 18% of patients treated with nivolumab monotherapy and 26% who had the combination.

Scherpereel also shared promising preliminary survival data from the overall trial thus far, as of data cutoff March 31, 2017, a secondary endpoint of the study. After a median follow-up of 10.4 months, median progression-free survival (PFS) in patients receiving nivolumab as monotherapy (N = 63) was 4.0 months versus 5.6 months in those who received the combination (N = 62). By comparison, Scherpereel noted, “With first-line chemotherapy, usually the PFS is about 6 months.”

“More interestingly,” he continued, “in the preliminary median overall survival assessment, we were able to measure a median overall survival of 10.4 months with nivolumab and a very outstanding result of not reached for the Nivo + Ipi arm.”

Side effects in both arms were generally mild, Scherpereel said. The most common were thyroid problems, colon inflammation, and rash. Severe side effects were more frequent in the combination arm compared with the monotherapy group (18% vs 10%, respectively). Three treatment-related deaths were reported when ipilimumab was added: 1 each of metabolic encephalopathy, fulminant hepatitis, and acute renal failure.

Mature survival, quality-of-life, and biomarker data from the MAPS-2 trial, as well as subgroup analyses, are expected to be presented next autumn.

“It’s still amazing that we’re seeing the use of checkpoint inhibitors and immunotherapy expanding beyond just melanoma to other cancers that we thought were not susceptible to the immune system,” noted ASCO Expert Michael S. Sabel, MD, FACS, commenting on the study at the press conference. “These are dramatic response rates for a very difficult-to-treat cancer with very limited options.”

Sabel added that positive results with checkpoint inhibitors to treat other tumor types like sarcoma, triple-negative breast cancer, GI malignancies, are being reported throughout ASCO this year. He stressed how this is a great example of how basic research in 1 cancer can expand across the field of oncology and why basic science in these arenas is critical. “The exponential explosion that you’re seeing with the checkpoint inhibitors across such a wide array of tumors shows the benefit of that type of research.”

Scherpereel A, Mazieres J, Greillier L, et al. Second or 3rd line nivolumab (Nivo) versus Nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: results of IFCT-1501 MAPS2 randomized phase II trial. J Clin Oncol. 2017;35 (suppl; abstr LBA8507).

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