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

• Published in: Cancers Vol. 15; no. 2; p. 409
• Main Authors: De Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Johannes J, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, De Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Van Not, Olivier J, Piersma, Djura, Van Rijn, Rozemarijn S, Stevense-den Boer, Marion, Van der Veldt, Astrid A M, Vreugdenhil, Gerard, Van den Eertwegh, Alfonsus J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.01.2023; MDPI
• Subjects: Clinical trials; Comorbidity; Medical prognosis; MEK inhibitors; Melanoma; Mutants; Mutation; Patients; PD-1 protein; Performance evaluation; Regression analysis; Statistical analysis; Survival; Toxicity; Netherlands; targeted therapy; adjuvant therapy; melanoma; immune checkpoint inhibition
• DOI: 10.3390/cancers15020409
• ISSN: 2072-6694

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.