Zelboraf first, then probably Yervoy
Ok, here's the scoop on metastatic melanoma, all info very new (like within the past 6-8 months).
There is a new therapy, this BRAF inhibitor Zelboraf, that has amazing results in most patients with metastatic melanoma whose tumor has this BRAF mutation. In the majority of patients, tumor burden shrinks dramatically-- ie, the doctors can make all those mets go away. The medication does not seem to have major toxicity. The catch is that the tumor typically eventually develops resistance to Zelboraf and starts to grow again, usually after 6-7 months. There is of course investigation underway to figure out ways to keep this resistance from developing, but at this stage, drug resistance must be anticipated.
There is a second new therapy, a human antibody marketed as Yervoy. This drug enhances the body's own immune response to the tumor. When you look at the stats, it seems to be only somewhat better than standard chemo- 7 months survival with standard chemo versuses 10 months with Yervoy (just Yervoy alone, not in combo with other drugs). However, hidden in those stats is that the fact that some patients respond extremely well to Yervoy. Twenty percent of patients receiving Yervoy alone are still alive at 3 years; it is reasonable to expect a better survival rate in patients treated with Yervoy in combo with other treatments. Yervoy seems to be best at keeping the tumor suppressed, not at shrinking it. The big negative to Yervoy is that it can have some unintended immune effects in the body, causing serious and even life threatening toxicity in some patients.
So the game plan is treat first with Zelboraf, then a pet scan in 2 months to see how much they've knocked back the mets. If they get the dramatic response they expected, then start Yervoy. The best possible outcome is to go cancer-free with the Zelboraf, then maintain that for years with the Yervoy.
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