Pharmacy and Pharmaceutical Sciences Commons^™

Short-Term Treatment With Multi-Drug Regimens Combining Braf/Mek-Targeted Therapy And Immunotherapy Results In Durable Responses In Braf-Mutated Melanoma, Michael G. White, Robert Szczepaniak Sloane, Russell G. Witt, Alexandre Reuben, Pierre Olivier Gaudreau, Miles C. Andrews, Ningping Feng, Sarah Johnson, Caleb Class, Christopher Bristow, Khalida Wani, Courtney Hudgens, Luigi Nezi, Teresa Manzo, Mariana Pettaccia De Macedo, Jianhua Hu, Richard Davis, Hong Jiang, Peter Prieto, Elizabeth Burton, Patrick Hwu, Hussein Tawbi, Jeffrey Gershenwald, Alexander J. Lazar, Michael T. Tetzlaff, Willem Overwijk, Scott E. Woodman, Zachary A. Cooper, Joseph R. Marszalek, Michael A. Davies, Timothy P. Heffernan, Jennifer A. Wargo

Scholarship and Professional Work – COPHS

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 …