Discontinuation of braf/mek-directed targeted therapy after complete remission of metastatic melanoma—a retrospective multicenter adoreg study

Henner Stege, Maximilian Haist*, Michael Schultheis, Maria Isabel Fleischer, Peter Mohr, Friedegund Meier, Dirk Schadendorf, Selma Ugurel, Elisabeth Livingstone, Lisa Zimmer, Rudolf Herbst, Claudia Pföhler, Katharina Kähler, Michael Weichenthal, Patrick Terheyden, Dorothee Nashan, Dirk Debus, Martin Kaatz, Fabian Ziller, Sebastian HaferkampAndrea Forschner, Ulrike Leiter, Alexander Kreuter, Jens Ulrich, Johannes Kleemann, Fabienne Bradfisch, Stephan Grabbe, Carmen Loquai

*Corresponding author for this work


The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.

Original languageEnglish
Article number2312
Issue number10
Publication statusPublished - 02.05.2021


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