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Cancer Treat Rev. 2014 Oct;40(9):1056-64. doi: 10.1016/j.ctrv.2014.06.012. Epub 2014 Jul 7.

Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma.

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Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, 375 Longwood Ave, Mailstop: MASCO 428, Boston, MA 02215, USA. Electronic address:
APHP Department of Dermatology, CIC, U976 Hôpital Saint-Louis University Paris Diderot, 1 Avenue Claude Vellefaux, Paris 75010, France. Electronic address:
Center for Immuno-Oncology, Melanoma Center, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address:
Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Siena 53100, Italy. Electronic address:
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address:
Ludwig Center for Cancer Immunotherapy, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. Electronic address:
Seattle Cancer Care Alliance, 825 Eastlake Ave E, G4-830, Seattle, WA 98109, USA. Electronic address:
Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address:


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.


Advanced melanoma; CTLA-4; Immunotherapy; Long-term survival; PD-1; Targeted therapy

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