Inês P Silva1, Georgina V Long. 1. aMelanoma Institute Australia, Sydney, Australia bRoyal North Shore, Sydney, Australia cMater Hospital, Sydney, Australia dUniversity of Sydney, Sydney, Australia.
Abstract
PURPOSE OF REVIEW: Here we review the results from relevant phase III trials and discuss treatment strategies for challenging subgroups of melanoma patients. RECENT FINDINGS: Targeted therapies induce rapid responses in the majority of BRAF-mutant patients, however, 50% of these responders will develop resistance within approximately 13 months. In contrast, inhibitors of checkpoints on T cells, particularly inhibitors of PD-1, induce responses in 40-55% of patients (monotherapy or whenever combined with anti-CTLA-4), and these responses tend to be durable. Data from subgroup analyses of large clinical trials, as well as patient-centred factors, help guide clinicians in their choice of first-line therapy. SUMMARY: Immune checkpoint inhibitors and MAP kinase pathway-targeted therapies have revolutionized the management of advanced melanoma, and significantly prolong the overall survival of patients with this disease. The median overall survival is over 2 years for both anti-PD-1-based therapy and combined BRAF and MEK inhibition. Without head-to-head comparison data for either therapy, choice of first-line drug treatment is difficult.
PURPOSE OF REVIEW: Here we review the results from relevant phase III trials and discuss treatment strategies for challenging subgroups of melanomapatients. RECENT FINDINGS: Targeted therapies induce rapid responses in the majority of BRAF-mutant patients, however, 50% of these responders will develop resistance within approximately 13 months. In contrast, inhibitors of checkpoints on T cells, particularly inhibitors of PD-1, induce responses in 40-55% of patients (monotherapy or whenever combined with anti-CTLA-4), and these responses tend to be durable. Data from subgroup analyses of large clinical trials, as well as patient-centred factors, help guide clinicians in their choice of first-line therapy. SUMMARY: Immune checkpoint inhibitors and MAP kinase pathway-targeted therapies have revolutionized the management of advanced melanoma, and significantly prolong the overall survival of patients with this disease. The median overall survival is over 2 years for both anti-PD-1-based therapy and combined BRAF and MEK inhibition. Without head-to-head comparison data for either therapy, choice of first-line drug treatment is difficult.
Authors: Michael B Atkins; Clara Curiel-Lewandrowski; David E Fisher; Susan M Swetter; Hensin Tsao; Julio A Aguirre-Ghiso; Maria S Soengas; Ashani T Weeraratna; Keith T Flaherty; Meenhard Herlyn; Jeffrey A Sosman; Hussein A Tawbi; Anna C Pavlick; Pamela B Cassidy; Sunandana Chandra; Paul B Chapman; Adil Daud; Zeynep Eroglu; Laura K Ferris; Bernard A Fox; Jeffrey E Gershenwald; Geoffrey T Gibney; Douglas Grossman; Brent A Hanks; Douglas Hanniford; Eva Hernando; Joanne M Jeter; Douglas B Johnson; Samir N Khleif; John M Kirkwood; Sancy A Leachman; Darren Mays; Kelly C Nelson; Vernon K Sondak; Ryan J Sullivan; Glenn Merlino Journal: Clin Cancer Res Date: 2021-01-07 Impact factor: 13.801
Authors: Dingyuan Hu; Daniel Ansari; Qimin Zhou; Agata Sasor; Katarzyna Said Hilmersson; Roland Andersson Journal: World J Surg Oncol Date: 2019-02-08 Impact factor: 2.754
Authors: Dan A Erkes; Weijia Cai; Ileine M Sanchez; Timothy J Purwin; Corey Rogers; Conroy O Field; Adam C Berger; Edward J Hartsough; Ulrich Rodeck; Emad S Alnemri; Andrew E Aplin Journal: Cancer Discov Date: 2019-12-03 Impact factor: 38.272