Immunotherapy is effective in the treatment of relapsed mesothelioma, according to results of the MAPS-2 phase II trial
Early findings from an ongoing phase II clinical trial in France, MAPS-2, show that immunotherapy may slow tumor growth in patients with malignant pleural mesothelioma (MPM) who relapsed on first-line chemotherapy, a setting where there are currently no effective treatment options. After 12 weeks, a disease control rate (DCR) of 44% was reported among patients treated with nivolumab and in 50% of the patients who received a combination of nivolumab and ipilimumab. These findings suggest that immunotherapy may provide new hope to patients with relapsed mesothelioma.
MPM is an aggressive and quite rare cancer that is associated with asbestos exposure. Currently there are no validated curative treatments for MPM. Moreover, there are no validated treatment options for patients beyond first-line pemetrexed-based chemotherapy. As a result, MPM patients failing 1st line chemotherapy have a very poor outcome with a DCR of less than 30% on 2nd line therapy and a median overall survival (OS) of only 6 to 9 months. Anti-tumor immunotherapy using immune checkpoint inhibitors may improve the prognosis of these patients, as suggested by preliminary data with the anti-PD-1 inhibitor pembrolizumab in mesothelioma.
This multi-center clinical trial enrolled 125 patients with advanced MPM who had received up to two prior treatments, including standard platinum-based chemotherapy. In order to be eligible for the study, patients had to be older than 18 years, have measurable disease and have an ECOG performance status of 0 or 1. The patients were randomly assigned to treatment with nivolumab (3mg/kg q2w), or nivolumab (3mg/kg q2w) plus ipilimumab (1mg/kg q6w), until progression or unacceptable toxicity. The majority of patients (80%) in the study were male, and the median age was 72 years. In total, 70% of patients received at least 3 cycles of either treatment.
During ASCO 2017, results were reported from the first 108 patients treated on the study. The DCR, defined as the percentage of patients with a complete or partial response and patients with stable disease, was 44% among the patients who received nivolumab only (23/54) and 50% among those who received nivolumab with ipilimumab (28/54). To set this in perspective, the 12-week DCR for all treatments previously tested in relapsed MPM was less than 30%. The overall response rate was 16.7% for patients treated with nivolumab (9/54) and 25.9% among those treated with nivolumab and ipilimumab (14/54). After a mean follow-up of 10.4 months, the median progression-free survival (PFS) among the 125 patients enrolled in the study was 4 months with nivolumab alone and 5.6 months with nivolumab and ipilimumab. The median OS was 10.4 months in the nivolumab group and was not yet reached in the nivolumab with ipilimumab group. The side effects were rather mild overall with the most common being thyroid problems, colon inflammation, and skin rash. Severe side effects were more common in the nivolumab plus ipilimumab group (18% vs. 10%), in which three treatment-related deaths occurred.
In summary, both nivolumab alone and ipilimumab plus nivolumab reached their 1st endpoint in the 2nd, or 3rd line treatment of MPM with meaningful increases in DCR after 12 weeks. In addition to this, patients in both arms seem to have a longer median OS than what was reported with other treatments in this setting. With 125 patients, MAPS-2 is the largest clinical trial of immune checkpoint inhibitors in mesothelioma to date. Many other ongoing clinical trials are also exploring nivolumab and other immune checkpoint inhibitors as second- or third-line treatments for MPM. In addition, several larger clinical trials investigating immune checkpoint inhibitors as initial therapy for MPM are already under way.
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 the IFCT-1501 MAPS2 randomized phase 2 trial. Presented at ASCO 2017; Abstract LBA8507.