Nivolumab or Nivolumab Plus Ipilimumab in Relapsed Malignant Pleural Mesothelioma
In a French phase II trial reported in The Lancet Oncology, Scherpereel et al found evidence of activity with nivolumab or the combination of nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma.
Study Details
In the open-label, noncomparative trial, 125 patients from 21 sites in France were randomly assigned between March and August 2016 to receive nivolumab (n = 63) or nivolumab plus ipilimumab (n = 62). Patients had to have disease progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease, and a life expectancy > 12 weeks. Patients received nivolumab at 3 mg/kg every 2 weeks or nivolumab plus ipilimumab at 1 mg/kg every 6 weeks, given until disease progression or unacceptable toxicity.
The primary outcome measure was the proportion of patients with 12-week disease control on masked independent central review. The primary endpoint was assessed in the first 108 eligible patients. Efficacy analyses were also performed in the intention-to-treat population.
Treatment Responses
In the first 108 eligible patients, 12-week disease control was observed in 24 patients (44%) in the nivolumab group and in 27 (50%) in the nivolumab-plus-ipilimumab group. In the intention-to-treat population, 12-week disease control was observed in 25 patients (40%) in the nivolumab group and 32 (52%) in the nivolumab-plus-ipilimumab group. Among the first 108 patients, objective response was observed in 10 patients (19%) in the nivolumab group and 15 (28%) in the combination group.
After a median follow-up of 20.1 months, median progression-free survival was 4.0 months in the nivolumab group and 5.6 months in the combination group, and median overall survival was 11.9 and 15.9 months, respectively.
Adverse Events
Grade 3 or 4 toxicities occurred in 14% of the nivolumab group and in 26% of the combination group, with the most common being asthenia (2% in nivolumab group vs 5% in combination group), increased aspartate aminotransferase or alanine aminotransferase (0% vs 7% of each), and lipase increase (3% vs 2%). No adverse events led to death in the nivolumab group; adverse events led to death in 3 patients in the combination group (due to fulminant hepatitis, encephalitis, and acute kidney failure).
The investigators concluded, “Nivolumab monotherapy or nivolumab plus … ipilimumab combination therapy both showed promising activity in relapsed patients with malignant pleural mesothelioma, without unexpected toxicity. These regimens require confirmation in larger clinical trials.”
Arnaud Scherpereel, PhD, of the Department of Pulmonary and Thoracic Oncology, University of Lille, University Hospital (CHU) of Lille, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the French Cooperative Thoracic Intergroup. The study authors' full disclosures can be found at thelancet.com.
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