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Unresectable and Metastatic Melanoma of the Skin: Literature Review of Clinical Trials and Efficacy Endpoints Since 2000

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Abstract

Advanced and metastatic melanoma has historically been one of the most difficult cancers to treat, with few treatment options. For over 20 years, dacarbazine chemotherapy was the only treatment approved by the US Food and Drug Administration for melanoma. In recent years, breakthroughs have been made in the areas of monoclonal antibody immunotherapies and genetically targeted therapies, leading to FDA approval of several new drugs for metastatic melanoma that have demonstrated improved patient response and survival. In an effort to understand the changing landscape of therapies for advanced and metastatic melanoma, we have reviewed 38 publicly available randomized clinical trials from http://ClinicalTrials.gov in metastatic and unresectable melanoma since the year 2000, to assess developments in the design and conduct of clinical trials over time and to compare the clinical efficacy of old and new therapies. We first present a brief history of FDA approvals of therapies for melanoma, followed by an exploration of trends in the patient population and demographics, eligibility criteria, and statistical methods of clinical trials over time. Next, we compare the efficacy results of old and new study treatments, examining the endpoints of progression-free survival, overall survival, and response rate. Overall, we find that the clinical trial population largely reflected the general population of patients with melanoma in demographic factors, with the exception of patient age. Our findings suggest that the developments of immunotherapies and targeted therapies have improved patient trial results on the discussed endpoints.

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Authors and Affiliations

  1. Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Building 21, Room 3673, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA

    Susan Jin MPH, Pallavi S. Mishra-Kalyani PhD & Rajeshwari Sridhara PhD

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  1. Susan Jin MPH
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  2. Pallavi S. Mishra-Kalyani PhD
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  3. Rajeshwari Sridhara PhD
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Correspondence to Susan Jin MPH.

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Jin, S., Mishra-Kalyani, P.S. & Sridhara, R. Unresectable and Metastatic Melanoma of the Skin: Literature Review of Clinical Trials and Efficacy Endpoints Since 2000. Ther Innov Regul Sci 53, 59–70 (2019). https://doi.org/10.1177/2168479018769286

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