• Selma Ugurel, Joachim Röhmel, Paolo A Ascierto, Keith T Flaherty, Jean Jacques Grob, Axel Hauschild, James Larkin, Georgina V Long, Paul Lorigan, Grant A McArthur, Antoni Ribas, Caroline Robert, Dirk Schadendorf, and Claus Garbe.
• Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de.
• Eur. J. Cancer. 2017 Sep 1; 83: 247-257.

AbstractThe treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan-Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials.Copyright © 2017 Elsevier Ltd. All rights reserved.

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