More people with advanced melanoma survive for two years or more when they receive a combination of two immunotherapy drugs given before a combination of two targeted therapies, if needed, compared to people who start treatment with targeted therapies. The finding comes from a clinical trial that was stopped early because definitive results became apparent sooner than expected. It provides strong evidence for how best to treat patients with melanoma that has a specific mutation: immunotherapy is the better initial approach even for people whose tumors have a mutation that could be treated by targeted therapies.