Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Melissa M De Meza, Willeke A M Blokx, Johannes J Bonenkamp, Christian U Blank, Maureen J B Aarts, Franchette W P J van den Berkmortel, Marye J Boers-Sonderen, Jan Willem B De Groot, John B A G Haanen, Geke A P Hospers, Ellen Kapiteijn, Olivier J Van Not, Djura Piersma, Rozemarijn S Van Rijn, Marion Stevense-den Boer, Astrid A M Van der Veldt, Gerard Vreugdenhil, Alfonsus J M Van den Eertwegh, Karijn P M Suijkerbuijk, Michel W J M Wouters

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Abstract

Adjuvant BRAF/MEK- and anti-PD-1 inhibition have significantly improved recurrence-free survival (RFS) compared to placebo in resected stage III BRAF-mutant melanoma. However, data beyond the clinical trial setting are limited. This study describes the toxicity and survival of patients treated with adjuvant BRAF/MEK inhibitors and compares outcomes to adjuvant anti-PD-1. For this study, stage III BRAF V600 mutant cutaneous melanoma patients treated with adjuvant BRAF/MEK-inhibition or anti-PD-1 were identified from the Dutch Melanoma Treatment Registry. BRAF/MEK- and anti-PD-1-treated patients were matched based on propensity scores, and RFS at 12 and 18 months were estimated. Between 1 July 2018 and 31 December 2021, 717 patients were identified. Of these, 114 patients with complete records were treated with BRAF/MEK therapy and 532 with anti-PD-1. Comorbidities (p = 0.04) and geographical region (p < 0.01) were associated with treatment choice. In 45.6% of BRAF/MEK-treated patients, treatment was prematurely discontinued. Grade ≥ 3 toxicity occurred in 11.5% of patients and was the most common cause of early discontinuation (71.1%). At 12 and 18 months, RFS in BRAF/MEK-treated patients was 85% and 70%, compared to 68% and 68% in matched anti-PD-1-treated patients (p = 0.03). In conclusion, comorbidities and geographical region determine the choice of adjuvant treatment in patients with resected stage III BRAF-mutant melanoma. With the currently limited follow-up, BRAF/MEK-treated patients have better RFS at 12 months than matched anti-PD-1-treated patients, but this difference is no longer observed at 18 months. Therefore, longer follow-up data are necessary to estimate long-term effectiveness.

Original languageEnglish
Article number409
Number of pages16
JournalCancers
Volume15
Issue number2
DOIs
Publication statusPublished - 7 Jan 2023

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