Weber JS, Haque W, Markovic SN, Salama AKS, Mehmi I, Sullivan RJ, Najjar YG, Van Akkool A, Menzies A, Long G, Taylor AM, Haanen J, Zijlker L, Davis KL, Karanth S, Shah RM, Connolly L, Norton D. Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant checkpoint inhibitor and subsequent surgical resection in patients with BRAF V600–mutated stage III/IV melanoma. Poster presented at the ESMO Congress 2023; October 22, 2023. Madrid, Spain.

In BRAF mutant resected melanoma, both targeted therapy and immunotherapy have shown durable clinical benefit as 1st line (1L) adjuvant therapy. However, there are no clinical studies evaluating 2nd line (2L) adjuvant targeted therapy in patients with locoregional relapse and complete surgical resection following initial adjuvant immunotherapy.

METHODS: This was a retrospective, multicenter chart review study of BRAF V600-mutated stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant checkpoint inhibitor therapy, then relapsed locoregionally or distantly, were again resected to NED, and then treated with dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS-2) after initiation of dab/tram therapy. Secondary endpoints included overall survival (OS) and distant metastasis-free survival (DMFS). Analyses were descriptive with event time endpoints (RFS-2, OS, DMFS) estimated using the Kaplan-Meier method.

RESULTS: A total of 37 patients were included (median age 51 years, 62% male, 89% stage III, median follow-up of 19 months from dab/tram initiation). Median time to dab/tram initiation after repeat resection to NED was 0.9 months (range: 0.2 – 2.8 months). A majority (73%) had discontinued dab/tram by last follow-up, with median therapy duration of 10.1 months (range: 1 day – 22.7 months). Median (95% confidence interval [CI]) RFS-2 was 18.9 (14.9 – 28.1) months, with 91% and 81% remaining relapse-free at 12 and 18 months, respectively; most patients also remained distant metastasis-free at 6 months (97%) and 12 months (85%). Only 2 patients were deceased at last follow-up, with nearly all patients (97%) still alive at 18 months; median OS was not reached.

CONCLUSIONS: More than 80% of patients remained relapse- and metastasis-free for at least 12 months after initiation of dab/tram. Longer follow-up and a larger patient cohort is needed in future studies to confirm efficacy of 2L adjuvant dab/tram in this population.

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