Short-term treatment with multi-drug regimens combining BRAF/MEK-targeted therapy and immunotherapy results in durable responses in

Targeted and immunotherapy regimens have revolutionized the treatment of advanced melanoma patients. Despite this, only a subset of patients respond durably. Recently, combination strategies of BRAF/MEK inhibitors with immune checkpoint inhibitor monotherapy (α-CTLA-4 or α-PD-1) have increased the rate of durable responses. Based on evidence from our group and others, these therapies appear synergistic, but at the cost of significant toxicity. We know from other treatment paradigms (e.g. hematologic malignancies) that combination strategies with multi-drug regimens (>4 drugs) are associated with more durable disease control. To better understand the mechanism of these improved outcomes, and to identify and prioritize new strategies for testing, we studied several multi-drug regimens combining BRAF/MEK targeted therapy and immunotherapy combinations in a

Informations de copyright

© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Déclaration de conflit d'intérêts

MCA reports advisory board participation and honoraria from Merck Sharp and Dohme, outside the submitted work. MAD has been a consultant to Roche/Genentech, Array, Novartis, BMS, GlaxoSmithKline (GSK), Sanofi-Aventis, Vaccinex and Apexigen, and he has been the PI of research grants to UT MD Anderson by Roche/Genentech, GSK, Sanofi-Aventis, Merck, Myriad, and Oncothyreon. JEG reports advisory board participation with Merck, Regeneron, BMS, Novartis, and Syndax. AJL reports personal fees from BMS, Novartis, Genentech/Roche, and Merck; personal fees and non-financial support from ArcherDX and Beta-Cat; grants and non-financial support from Medimmune/AstraZeneca and Sanofi; grants, personal fees and non-financial support from Janssen, all outside the submitted work. MTT reports personal fees from Myriad Genetics, Seattle Genetics and Novartis, all outside the submitted work. ZAC is currently an employee of AstraZeneca outside the submitted work. JAW reports speaker fees from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune and BMS; consultant/advisor roles or advisory board membership for Roche-Genentech, Novartis, AstraZeneca, GSK, BMS, Merck/MSD, Biothera Pharma, and Microbiome DX; and receives clinical trial support from GSK, Roche-Genentech, BMS, and Novartis, all outside the current work. The remaining authors declare no competing interests.