Liver Toxicity Brings Melanoma Study on Bristol-Myers Squibb Company/Roche Drugs to a Halt

Published: Apr 04, 2013

Unexpected liver toxicity derailed a phase I melanoma trial of concurrent treatment with the first two targeted agents approved for the disease, according to a brief communication from investigators. Four of the first six patients treated with vemurafenib (Zelboraf) and ipilimumab (Yervoy) developed grade 2 or 3 elevations of aminotransferase (ALT), as did three of the first four patients in a second six-patient cohort. One patient in each cohort had grade 2 or 3 bilirubin elevations along with elevated ALT. All cases of hepatotoxicity resolved with temporary discontinuation of the study drugs or administration of glucocorticoids. Nonetheless, investigators closed the trial after the last two patients in the second cohort were treated with ipilimumab alone, as reported online in the New England Journal of Medicine. "The results of this phase I study highlight the risk of concurrent administration of vemurafenib and ipilimumab," Jedd Wolchok, MD, PhD, of Memorial Sloan-Kettering Cancer Center in New York City, and co-authors concluded in a letter to the journal editors.

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