Immunotherapy Yields ‘Dramatic’ Response Rates in Relapsed Mesothelioma

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CHICAGO-Immunotherapy may represent an effective new treatment approach for relapsed mesothelioma patients, according to a new study.

Anti–programmed death-1 (PD-1) immunotherapy may have activity as second- or third-line therapy in malignant pleural mesothelioma (MPM), an aggressive, rare cancer associated with asbestos exposure that has no curative treatment. All MPM patients relapse despite initial chemotherapy, and median overall survival (OS) is 9 months at most, said lead author Arnaud Scherpereel, MD, PhD, head of the pulmonary and thoracic oncology department at the University Hospital (CHU) of Lille in Lille, France, at a press briefing at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract LBA8507).

In a multicenter, randomized, non-comparative phase II trial, Scherpereel and colleagues enrolled 125 patients, median age 72 years, with advanced MPM who had received up to two prior treatments, including standard platinum-based chemotherapy. The patients were randomly assigned to treatment with nivolumab 3 mg/kg once every 2 weeks or the same dose of nivolumab plus ipilimumab 1 mg/kg every 6 weeks until progression or unacceptable toxicity. Some 70% or more patients received 6 cycles of treatment.

In the first 108 eligible patients treated, the 12-week disease control rate (DCR) was 44% among the patients who received nivolumab only and 50% among those who received nivolumab plus ipilimumab. The 12-week DCR for all treatments previously tested in relapsed MPM was less than 30%, Scherpereel noted. Tumors shrank in 18% of patients treated with nivolumab monotherapy and 26% of those treated with nivolumab plus ipilimumab.

After a mean follow-up of 10.4 months, progression-free survival was 4 months with nivolumab alone and 5.6 months with nivolumab plus ipilimumab. The median OS was 10.4 months in the nivolumab group and not reached in the nivolumab plus ipilimumab group, “an outstanding result,” he said, noting that the median OS in both arms seems to be longer than all previous reports in this setting.

The side effects were mild overall, said Scherpereel, most commonly thyroid problems, colon inflammation, and skin rash. Several side effects were slightly more common in the nivolumab plus ipilimumab group (18% vs 10%); 3 treatment-related deaths occurred in the combination arm (1 metabolic encephalopathy, 1 fulminant hepatitis, and 1 acute renal failure).

“Both nivolumab alone and nivolumab plus ipilimumab reached their first endpoint in second- and third-line MPM patients, increasing meaningfully the 12-week DCR,” said Scherpereel, who noted that it’s too early to say whether the combination is better than nivolumab alone. “Immunotherapy may provide new therapeutic options as second- or third-line treatment for relapsing MPM patients.”

Ongoing clinical trials are exploring nivolumab and other immune checkpoint inhibitors as second- or third-line treatments for MPM. Also, several larger clinical trials investigating immune checkpoint inhibitors as initial therapy for MPM are under way.

ASCO Expert Michael S. Sabel, MD, of the University of Michigan Health Systems, commented: “This study shows dramatic response rates and the potential of immunotherapy in mesothelioma. We’re seeing a second wave of immunotherapy with expansion of its use in more cancer types.”