Michele Maio, MD
In the randomized phase IIB DETERMINE trial, the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) inhibitor tremelimumab did not improve overall survival vs placebo as second- or third-line treatment of relapsed malignant mesothelioma. These findings were reported in The Lancet Oncology by Michele Maio, MD, of the University Hospital of Siena, Istituto Toscano Tumori, and colleagues.
In the double-blind trial, 571 patients from 105 sites in 19 countries were randomized 2:1 between May 2013 and December 2014 to receive intravenous tremelimumab at 10 mg/kg (n = 382) or placebo (n = 189) every 4 weeks for 7 doses and every 12 weeks thereafter. The primary endpoint was overall survival in the intention-to-treat population.
Overall Survival and Toxicity
As of the data cutoff in January 2016, death had occurred in 80% of the tremelimumab group and 81% of the placebo group. Median overall survival was 7.7 months vs 7.3 months (hazard ratio = 0.92, P = .41). In a subgroup analysis, hazard ratios (all nonsignificant) were 0.90 in the second-line setting, 1.00 in the third-line setting, 0.70 in disease stage ≤ III, and 1.03 in disease stage IV.
Adverse events of grade ≥ 3 occurred in 65% of the tremelimumab group and 48% of the placebo group, with the most common being diarrhea (15% vs < 1%), dyspnea (9% vs 14%), and colitis (7% vs 0%). The most common serious adverse events were diarrhea (18% vs < 1%), dyspnea (8% vs 13%), and colitis (6% vs 0%). Adverse events led to death in 9% vs 6% of patients and were considered related to treatment in 1% vs 0%.
The investigators concluded: “Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors. Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing.” ■