Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma. Issue 12 (4th March 2023)

• Record Type: Journal Article
• Authors: van Duin, Isabella A. J.; Elias, Sjoerd G.; van den Eertwegh, Alfonsus J. M.; de Groot, Jan Willem B.; Blokx, Willeke A. M.; van Diest, Paul J.; Leiner, Tim; Verhoeff, Joost J. C.; Verheijden, Rik J.; van Not, Olivier J.; Aarts, Maureen J. B.; van den Berkmortel, Franchette W. P. J.; Blank, Christian U.; Haanen, John B. A. G.; Hospers, Geke A. P.; Kamphuis, Anna M.; Piersma, Djura; van Rijn, Rozemarijn S.; van der Veldt, Astrid A. M.; Vreugdenhil, Gerard; Wouters, Michel W. J. M.; Stevense‐den Boer, Marion A. M.; Boers‐Sonderen, Marye J.; Kapiteijn, Ellen; Suijkerbuijk, Karijn P. M.
• Is Part Of: International journal of cancer. Volume 152:Issue 12(2023)
• Page Start: 2493
• Page End: 2502
• Publication Date: 2023-03-04
• Subjects: BRAF(/MEK) inhibition -- immune checkpoint inhibition -- immunotherapy -- melanoma -- prognosis; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.34479
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune‐surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first‐line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression‐free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti‐PD‐1‐based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI‐treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years ( P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first‐line ICI or targeted therapy. Abstract : What's new? Time to first distant recurrence (TFDR) in melanoma can be long, probably due to effective immune surveillance. Patients with long TFDR potentially survive longer upon presentation with metastases, though evidence supporting this association is currently scant. Here, the association between TFDR and survival was examined among Dutch patients with advanced melanoma. Survival was found to be prolonged in patients with longer TFDR. This association was observed in patients treated with immune checkpoint inhibitiors and in patients treated with BRAF(/MEK) inhibitors. The study identifies TFDR as a novel factor for consideration in prognostic assessment of advanced melanoma.