Original Articles: Clinical ResearchBRAF and MEK inhibitors rechallenge as effective treatment for patients with metastatic melanomaCybulska-Stopa, Bożenaa,,*; Rogala, Pawełb,,*; Czarnecka, Anna M.b,,c; Galus, Łukaszd,,e; Dziura, Robertf; Rajczykowski, Marcing; Kubiatowski, Tomaszh; Wiśniewska, Magdalenai,,j; Gęga-Czarnota, Adriannak; Teterycz, Pawełb; Ziobro, Mareka; Suwiński, Rafałg; Mackiewicz, Jacekd,,l,,m; Rutkowski, PiotrbAuthor Information aClinical Oncology Clinic, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Krakow bDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology cDepartment of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw dDepartment of Medical and Experimental Oncology, Heliodor Swiecicki Clinical Hospital, University of Medical Sciences eChemotherapy Department, Greater Poland Cancer Centre, Poznan fClinical Oncology Clinic, Holy Cross Cancer Center, Kielce gDepartment of Radiotherapy and Chemotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice hClinical Oncology Department, Center of Oncology of the Lublin Region St. Jana z Dukli, Lublin iDepartment of Oncology and Brachytherapy Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun jDepartment of Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz kClinical Oncology Department, Beskid Oncology Center, Bielsko-Biala lDepartment of Biology and Environmental Studies, University of Medical Sciences mDepartment of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland *Bożena Cybulska-Stopa and Paweł Rogala contributed equally to the writing of this article. Received 4 December 2019 Accepted 7 February 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Bożena Cybulska-Stopa, MD, PhD, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, ul. Garncarska 11, 31-115 Krakow, Poland, Tel: +48 12 63 48 260; e-mail: email@example.com Melanoma Research: October 2020 - Volume 30 - Issue 5 - p 465-471 doi: 10.1097/CMR.0000000000000662 Buy SDC Metrics Abstract Despite considerable progress made in the treatment of patients with advanced melanoma, the majority of the patients treated with BRAF and mitogen-activated protein inhibitors (BRAFi and MEKi) experience a disease progression due to acquired resistance. Currently, ongoing studies explore the possibility to overcome or reverse this process. Our multicenter retrospective analysis included 51 patients with metastatic BRAF-mutated melanoma who had previously progressed on BRAFi/MEKi than had progressed on immunotherapy (anti-progression disease-1 or anti-cytotoxic T-lymphocyte-associated protein 4) and next were rechallenged with BRAFi/MEKi. Median age at BRAFi/MEKi rechallenge was 56 (range: 31–82 y/o). Median overall survival from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 29.7 and 9.3 months, respectively, whereas median progression-free survival was 10.5 and 5.9 months, respectively. Six-month, annual, and 2-year overall survival rates on both treatments were: 98% and 55%, 92% and 29%, and 69% and 2%, respectively. A response rate to treatment was higher in the group receiving BRAFi/MEKi for the first time as compared with the group receiving BRAFi/MEKi rechallenge and was overall response rate 72% and 27%; disease control rate 92% and 63%. Time interval between the end of the first BRAFi/MEKi treatment and the beginning of BRAFi/MEKi rechallenge did not influence median overall survival or progression-free survival. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. BRAFi/MEKi rechallenge treatment remains clinically important and is associated with the lower toxicity. BRAFi/MEKi rechallenge efficacy is higher in patients who are in good performance status, with normal lactate dehydrogenase, and without brain metastases. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.