Phase 3 Trial Update of Ipilimumab + Dacarbazine for Metastatic Melanoma

(ChemotherapyAdvisor) – Ipilimumab (Yervoy) offers 4- and 5-year survival benefits for patients with metastatic melanoma, according to long-term follow-up analyses of a Phase 3 and several Phase 2 clinical trials reported by Bristol-Myers Squibb at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna, Austria.

“Results from these investigational studies showed a prolonged survival benefit with Yervoy at 4 and 5 years for some patients,” reported Celeste Lebbe, MD, Professor of Dermatology, Hôpital Saint-Louis in Paris, France. “These results add to the growing body of long-term survival data seen in some patients treated with Yervoy and further our understanding of the potential of this immunotherapy in the treatment of metastatic melanoma."

In the double-blind, randomized Phase 3 trial, 502 treatment-naïve patients with Stage III unresectable or Stage IV metastatic melanoma were randomized to receive ipilimumab (10mg/kg) plus dacarbazine (DTIC; Bayer) 850mg/m2 or DTIC alone. Follow-up analysis identified a 4-year survival rate among ipilimumab-arm patients of 19% (95% CI: 14.2%–24.2%) vs. 9.6% (95% CI: 6.1–13.5) among patients receiving DTIC alone, the authors reported.

Follow-up data from three Phase 2 trials, representing 487 patients, found 5-year survival rates of 38% to 49% among treatment-naïve patients who were administered ipilimumab, and 12% to 28% among non-treatment-naïve patients, the authors reported.

Ipilimumab “can result in severe and fatal immune-related adverse reactions due to T-cell activation and proliferation,” the authors cautioned.

“The combination of DTIC with Yervoy is not an FDA approved-regimen,” the authors noted. Nor were the analyses designed to compare the safety and efficacy of the FDA-approved monotherapy dose of 3mg/kg for unresectable or metastatic melanoma versus the investigational dose of 10mg/kg, they added.

Metastatic melanoma is an aggressive cancer with a historical 5-year survival rate of <10% in patients with metastatic disease, Dr. Lebbe noted.

Ipilimumab is a recombinant human monoclonal antibody and the first FDA-approved cancer immunotherapy that blocks the cytotoxic T- lymphocyte antigen-4 (CTLA-4), a negative regulator of T-cell activation. 

Abstracts (#1116PD and #1117PD)

Abstract (#1127, Phase 3)