Chemoprevention Agents for Melanoma: A Path Forward into Phase III Clinical Trials

• Published in: Cancer 2018-10, Vol.125 (1), p.18-44
• Main Authors: Jeter, Joanne, Bowles, Tawnya, Curiel-Lewandrowski, Clara, Swetter, Susan M., Filipp, Fabian V., Abdel-Malek, Zalfa, Geskin, Larisa J., Brewer, Jerry D., Arbiser, Jack L., Gershenwald, Jeffrey E., Chu, Emily Y., Kirkwood, John, Box, Neil F., Funchain, Pauline, Fisher, David E., Kendra, Kari, Marghoob, Ashfaq, Chen, Suephy C., Ming, Michael E., Albertini, Mark R., Vetto, John T., Margolin, Kim A., Pagoto, Sherry, Hay, Jennifer, Grossman, Douglas, Ellis, Darrel L., Kashani-Sabet, Mohammed, Mangold, Aaron R., Markovic, Svetomir, Meyskens, Frank L., Nelson, Kelly, Powers, Jennifer G., Robinson, June K., Sahni, Debjani, Sekulic, Aleksandar, Sondak, Vernon K., Wei, Maria L., Zager, Jonathan S., Dellavalle, Robert P., Thompson, John A., Weinstock, Martin A., Leachman, Sancy A., Cassidy, Pamela B.
• Format: Article
• Language: English
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31719

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival. As these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge towards the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to dramatically reduce both the morbidity and high costs associated with treating patients with metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group comprised of National Cancer Trials Network (NCTN) participants, discuss research aimed at discovering and developing (or re-purposing) drugs and natural products for the prevention of melanoma, and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, pre-clinical data, epidemiological evidence and results of available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies are also considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and likelihood that a given compound might be a suitable candidate for a Phase III clinical trial within the next 5 years. In this work, experts from the national Melanoma Prevention Working Group, 156 , 157 comprised of National Cancer Trials Network participants, discuss mechanisms of action, preclinical data, epidemiologic evidence, and results from available clinical trials for the most promising melanoma chemoprevention agents. Furthermore, the work provides an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.