Historically, the median overall survival for patients with stage IV
melanoma was less than 1 year and the 5-year survival rate was ∼10%. Recent advances in
therapy have raised 5-year survival expectations to ∼20%. Notably, a subset of
melanoma patients who receive
immunotherapy with high-dose
interleukin-2, and now
ipilimumab, can achieve long-term survival of at least 5 years. A major goal in
melanoma research is to increase the number of patients who experience this overall survival benefit. In this review, we discuss the attributes of
immunotherapy and newer targeted agents, and consider how combination strategies might improve the chances of achieving durable benefit and long-term survival. We also discuss three areas that we believe will be critical to making further advances in
melanoma treatment. To better understand the clinical profile of patients who achieve long-term survival with
immunotherapy, we first present data from
ipilimumab clinical trials in which a subset of patients experienced durable responses. Second, we discuss the limitations of traditional metrics used to evaluate the benefits of
immunotherapies. Third, we consider emerging issues that clinicians are currently facing when making treatment decisions regarding
immunotherapy. A better understanding of these novel treatments may improve survival outcomes in
melanoma, increase the number of patients who experience this overall survival benefit, and inform the future use of these agents in the treatment of other
cancer types.