Hopes for a quick one-two punch against melanoma have hit a snag. A Phase I trial testing Bristol-Myers Squibb's Yervoy and Roche's Zelboraf in melanoma patients was stopped after signs of liver toxicity developed in several patients.
As the researchers reported online in the New England Journal of Medicine, four of the first 6 patients treated showed signs of liver toxicity, with significantly elevated enzyme levels. Among a second group of 6, who were treated with a lower dose of Zelboraf and the same dose of Yervoy, two experienced significantly elevated levels of enzymes and bilirubin.
The results were unexpected because Yervoy and Zelboraf patients rarely experience liver problems significant enough to limit their use, the researchers said. "[A]mple rationale exists to investigate combined therapy with these two agents," they wrote.
Actually, people started talking about combining the two drugs even before they were both approved. Roche ($RHHBY) and Bristol-Myers ($BMY) teamed up to test them together. Some doctors have already used the two drugs in tandem.
But these study results "highlight the risk" of combining the two, the researchers wrote in their letter to the NEJM editor. "Our findings reinforce the need for carefully conducted trials of new combination therapies, even when both agents have regulatory approval and have distinct mechanisms of action," they wrote.