Scherpereel A, et al. - Researchers performed a prospective evaluation of the anti-programmed cell death 1 (PD-1) monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma. According to findings, promising activity of both anti-PD-1 nivolumab monotherapy or nivolumab plus anti-CTLA-4 ipilimumab combination therapy was seen in relapsed patients with malignant pleural mesothelioma. No unexpected toxicity was reported.

Methods

• Researchers performed this multicenter randomized, non-comparative, open-label, phase 2 trial at 21 hospitals in France.
• Patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1, histologically proven malignant pleural mesothelioma progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease by CT, and life expectancy greater than 12 weeks were considered eligible for inclusion in this trial.
• Random allocation (1:1) of participants to intravenous nivolumab (3 mg/kg bodyweight) every 2 weeks, or intravenous nivolumab (3 mg/kg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks), was done and treatment was administered until progression or unacceptable toxicity.
• Using a minimization method with a 0.8 random factor, central randomization stratified by histology (epithelioid vs non-epithelioid), treatment line (second line vs third line), and chemosensitivity to previous treatment (progression ≥3 months vs <3 months after pemetrexed treatment) was carried out.
• Evaluated by masked independent central review, the proportion of patients who achieved 12-week disease control was considered as the primary outcome; the primary endpoint would be met if disease control was achieved in at least 40% of patients.
• The first 108 eligible patients were assessed for the primary endpoint.
• Efficacy analyses in the intention-to-treat population were carried out.
• Including all patients who received at least one dose of their assigned treatment, they also performed safety analyses.

Results

• A total of 125 eligible patients were recruited and treated with either nivolumab (n=63) or nivolumab plus ipilimumab (n=62) between March 24 and August 25, 2016.
• In the first 108 eligible patients, 24 (44%; 95% CI 31–58) of 54 patients in the nivolumab group and 27 (50%; 37–63) of 54 patients in the nivolumab plus ipilimumab group achieved 12-week disease control.
• A total of 25 (40%; 28–52) of 63 patients in the nivolumab group and 32 (52%; 39–64) of 62 patients in the combination group achieved 12-week disease control in the intention-to-treat population.
• Grade 3–4 toxicities were observed in 9 (14%) of 63 patients in the nivolumab group and 16 (26%) of 61 patients in the combination group.
• Asthenia (one [2%] in the nivolumab group vs three [5%] in the combination group), asymptomatic increase in aspartate aminotransferase or alanine aminotransferase (none vs four [7%] of each), and asymptomatic lipase increase (two [3%] vs one [2%]) were the grade 3 adverse events that were most frequently experienced.
• In the nivolumab group, no toxicity-related death was reported, whereas three (5%) of 62 in the combination group died due to toxicities (one fulminant hepatitis, one encephalitis, and one acute kidney failure).