Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study

• Published in: International journal of cancer Vol. 155; no. 8; pp. 1455 - 1465
• Main Authors: Bloem, Manja, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, Bonenkamp, Johannes J, de Groot, Jan-Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, de Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.10.2024
• Subjects: Adjuvant therapy; Adjuvants; Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant - methods; Clinical outcomes; Female; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Male; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - mortality; Melanoma - pathology; Melanoma, Cutaneous Malignant; Metastases; Metastasis; Middle Aged; Mutation; Netherlands - epidemiology; Patients; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Prospective Studies; Registries; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Survival; Survival analysis; Netherlands; melanoma; acral melanoma; immune checkpoint inhibitors; adjuvant; immunotherapy
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.35060

Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HR 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM.