Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Rawa K. Ismail, Karijn P.M. Suijkerbuijk, Anthonius de Boer, Maaike van Dartel, Doranne L. Hilarius, A. M.G. Pasmooij, Michiel C.T. van Zeijl, Maureen J.B. Aarts, Franchette W.P.J. van den Berkmortel, Christian U. Blank, Marye J. Boers-Sonderen, Jan W.B. de Groot, John B.A.G. Haanen, Geke A.P. Hospers, Ellen Kapiteijn, Djura Piersma, Rozemarijn S. van Rijn, Astrid A.M. van der Veldt, Art Vreugdenhil, Hans WestgeestAlfons J. van den Eertwegh, Michel W.J.M. Wouters

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Recent results of patients with advanced melanoma treated with first-line BRAF-MEK inhibitors in clinical trials showed 5-year survival in one-third of patients with a median overall survival (OS) of more than 2 years. This study aimed to investigate these patients' real-world survival and identify the characteristics of long-term survivors. The study population consisted of patients with advanced cutaneous melanoma with a BRAF-V600 mutated tumor who were treated with first-line BRAF-MEK inhibitors between 2013 and 2017. Long-term survival was defined as a minimum OS of 2 years from start therapy. The median progression-free survival (mPFS) and median OS (mOS) of real-world patients ( n  = 435) were respectively 8.0 (95% CI, 6.8-9.4) and 11.7 (95% CI, 10.3-13.5) months. Two-year survival was reached by 28% of the patients, 22% reached 3-year survival and 19% reached 4-year survival. Real-world patients often had brain metastases (41%), stage IV M1c disease (87%), ECOG PS ≥2 (21%), ≥3 organ sites (62%) and elevated LDH of ≥250 U/I (49%). Trial-eligible real-world patients had an mOS of 17.9 months. Patients surviving more than 2 years ( n  = 116) more often had an ECOG PS ≤1 (83%), normal LDH (60%), no brain metastases (60%), no liver metastases (63%) and <3 organ sites (60%). Long-term survival of real-world patients treated with first-line BRAF-MEK inhibitors is significantly lower than that of trial patients, which is probably explained by poorer baseline characteristics of patients treated in daily practice. Long-term survivors generally had more favorable characteristics with regard to age, LDH level and metastatic sites, compared to patients not reaching long-term survival.

Original languageEnglish
Pages (from-to)460-468
Number of pages9
JournalMelanoma Research
Issue number6
Publication statusPublished - 1 Dec 2022

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Publisher Copyright: Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.


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