Immune Checkpoint Inhibition Shows Promise in Relapsing Malignant Pleural Mesothelioma

Immune Checkpoint Inhibition Shows Promise in Relapsing Malignant Pleural Mesothelioma

Dr. Arnaud Scherpereel presents Abstract 8507.
Both nivolumab alone and in combination with ipilimumab resulted in a promising disease control rate in patients with relapsing malignant pleural mesothelioma (MPM), according to the results of Abstract LBA8507.

“MPM is an aggressive and quite rare cancer without any validated curative treatment,” Arnaud Scherpereel, MD, PhD, of University Hospital of Lille, in France, said. Pemetrexed cisplatin is used as first-line therapy. Recent studies have shown that antiangiogenic agents can improve results, but after chemotherapy failure there is no validated subsequent option and disease control rates (DCRs) are usually under 30%.

There is, however, a strong rationale for the use of immune checkpoint inhibition in this malignancy. PD-L1 expression is associated with poor outcomes, and early trials had promising results with anti–PD-1/L1 agents with and without anti–CTLA-4 inhibition.

MAPS-2 was a noncomparative phase II trial including 125 patients randomly assigned to receive either nivolumab monotherapy (63 patients) or nivolumab plus ipilimumab (62 patients, 61 received treatment). All patients had unresectable MPM with documented progression after one or two previous lines of chemotherapy, including a pemetrexed/platinum doublet.

The study met its primary endpoint of DCR, which was assessed after 12 weeks. In the first 108 eligible patients, the DCR with nivolumab was 44.4% (18.5% with an objective response, 25.9% with stable disease); with the combination regimen, it was 50.0% (25.9% with objective response, 24.1% with stable disease). In the full intention-to-treat (ITT) population, these rates were 39.7% and 51.6%, respectively.

After 10.4 months of follow-up, the ITT population’s median progression-free survival was 4.0 months with nivolumab, and 5.6 months with nivolumab plus ipilimumab. The median overall survival was 10.4 months with nivolumab monotherapy, and has not been reached with the combination regimen.

In the nivolumab arm, 77.8% of patients experienced at least one drug-related adverse event (AE) of any grade; six patients (9.5%) had a grade 3/4 AE. Among patients in the nivolumab/ipilimumab group, 86.9% experienced an AE of any grade, and 11 patients (18.0%) had a grade 3/4 AE. There were three treatment-related deaths during the study, all in the combination group: one due to fulminant hepatitis, one due to encephalitis, and one due to acute kidney failure that occurred after 12 weeks.

There was a higher incidence of diarrhea (19.7% vs. 6.3%; p = 0.035) and pruritus (11.5% vs. 1.6%; p = 0.04) in the nivolumab/ipilimumab group. Dr. Scherpereel described the toxicity in both groups as manageable.

Dr. Anne S. Tsao discusses Abstract 8507.
“Both nivolumab alone and nivolumab plus ipilimumab reached their [primary] endpoint in second- and third-line MPM patients, increasing meaningfully the 12-week DCR,” Dr. Scherpereel said. “Moreover, patients from both arms of this study seem to have prolonged median [overall survival] than all previous reports in this setting. Immunotherapy may provide new therapeutic options as second- and third-line treatment for patients [with relapsing MPM].”

Session discussant Anne S. Tsao, MD, of The University of Texas MD Anderson Cancer Center, noted that the follow-up period was relatively short and that approximately 30% of patients in each group did not reach the third cycle of therapy. It will be important to know, she said, whether this was because of clinical progression or toxicity.

“The immune checkpoint inhibitors are likely to change our standard of care in mesothelioma,” Dr. Tsao said. “But we have to identify the population that benefits the most.” She noted that this study suggests an improvement with the combined PD-1/CTLA-4 inhibition in spite of the lack of power to directly compare, but a trial making such a direct comparison is likely needed. Dual inhibition “could be more beneficial in certain subgroups, and it may have higher efficacy in the front-line setting,” she said.  

–Dave Levitan