Response to encorafenib and binimetinib therapy after prior treatment with targeted therapy and immunotherapy in melanoma patient with brain metastases
Abstract
Brain metastases in melanoma patients are a serious therapeutic problem significantly worsening the prognosis. According to the literature, they occur in about 30–40% of patients. The subject of this study is a 53 year old patient with dissemination of melanoma to the central nervous system, who remains under systemic treatment at the Department of Clinical and Experimental Oncology in Poznań. The patient has been treated with targeted therapy with vemurafenib and cobimetinib, immunotherapy with pembrolizumab, and then again with targeted therapy (encorafenib with binimetinib) and immunotherapy with ipilimumab and nivolumab. Despite the poorer prognosis of patients with CNS metastases and less effective therapies, the patient remains in treatment for 6 years. Progression free survival (PFS) for targeted therapy in the first line of treatment and immunotherapy in the second line exceeded 20 months for each of these, while for rechallenge therapy with BRAF and MEK inhibitors (encorafenib with binimetinib) it was 15 months and nearly 3 times exceeded the median PFS obtained in retrospective analyzes of patients undergoing such treatment. In order to select patients with a poor prognosis (M1d) who nevertheless respond well and permanently to the therapy, it is advisable to find appropriate predictive biomarkers.
Keywords: melanomatargeted therapyBRAF inhibitorsMEK inhibitorsbrain metastasesrechallenge
References
- Long G, Atkinson V, Lo S, et al. Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases. Presented at: 2021 ASCO Annual Meeting Chicago, Illinois, June 4-8, 2021.
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019; 381(16): 1535–1546.
- Tawbi HA, Forsyth PA, Algazi A, et al. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018; 379(8): 722–730.
- Davies M, Saiag P, Robert C, et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017; 18(7): 863–873.
- Luther C, Swami U, Zhang J, et al. Advanced stage melanoma therapies: Detailing the present and exploring the future. Crit Rev Oncol Hematol. 2019; 133: 99–111.
- Marquez Rodas et al. Streszczenie 1038MO, ESMO 2021.
- Seghers AC, Wilgenhof S, Lebbé C, et al. Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor. Melanoma Res. 2012; 22(6): 466–472.
- Valpione S, Carlino MS, Mangana J, et al. Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study. Eur J Cancer. 2018; 91: 116–124.
- Cybulska-Stopa B, Rogala P, Czarnecka AM, et al. BRAF and MEK inhibitors rechallenge as effective treatment for patients with metastatic melanoma. Melanoma Res. 2020; 30(5): 465–471.