(ChemotherapyAdvisor) – First-line tremelimumab (CP-675206) did not increase overall survival (OS) when compared with standard-of-care chemotherapy in patients with metastatic melanoma, a phase 3 randomized trial reported in the Journal of Clinical Oncology online January 7, 2013.

Previously, the cytotoxic T lymphocyte–associated antigen-4 (CTL4)–blocking monoclonal antibody, tremelimumab, had induced durable responses in phase 1/2 studies in a subset of patients with advanced melanoma, noted Antoni Ribas, MD, of the Division of Hematology-Oncology, UCLA Medical Center, Los Angeles, CA, and colleagues.

In this study, they evaluated OS and other efficacy and safety end points in 655 patients with treatment-naive, unresectable stage IIIc or IV melanoma who were randomly assigned to tremelimumab 15 mg/kg once every 90 days or physician’s choice of standard-of-care chemotherapy (temozolomide or dacarbazine).

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At the second interim analysis after 340 deaths, the test statistic crossed the prespecified futility boundary. Survival follow-up continued; at 534 events, median OS was 12.6 months (95% CI: 10.8−14.3) for tremelimumab and 10.7 months (95% CI: 9.36−11.96) for chemotherapy (HR 0.88; P=0.127).

Objective response rate was 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 vs. 13.7 months; P=0.0011).

In the tremelimumab arm, the most common treatment-related adverse events were diarrhea, pruritus, and rash, and 7.4% had endocrine toxicities. There were seven treatment-related deaths in the tremelimumab arm and one in the chemotherapy arm.

“Tremelimumab induces a low-frequency but reproducible durable response rate in patients with metastatic melanoma,” the authors concluded. “Patient selection, dosing regimen, and use of another CTLA4-blocking agent (ipilimumab) as salvage therapy for patients in the comparator arm may explain the differences between the results of this phase 3 trial and those of two positive phase 3 trials with ipilimumab.”