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.