The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progressionfree (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 realworld 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