Real-World Treatment Patterns in Advanced Cutaneous Melanoma in the USA

Melanoma has an excellent prognosis when detected at a localized stage, but when patients present with regional or distant metastases, 5-year survival decreases to approximately 76% and 35%, respectively. Although recent advances in systemic therapies have improved outcomes for patients with advanced melanoma, these treatments are often not curative, and many patients ultimately develop disease progression requiring subsequent lines of therapy.

This study aimed to characterize real-world treatment patterns among patients in the USA with advanced cutaneous melanoma who transitioned from first-line (1L) to second-line (2L) systemic therapy.

This retrospective, observational study used administrative claims data from a large US managed care database. Adult patients with metastatic melanoma who initiated 1L systemic therapy between January 2023 and December 2025 and subsequently received 2L therapy were included. Claims-based algorithms identified treatment regimens by line of therapy. Sankey diagrams illustrate treatment transitions overall and by BRAF V600 mutation status.

Of 1772 patients who met study criteria, 680 (38.4%) were classified as presumed BRAF V600-mutated (BRAFmut) on the basis of treatment exposure, and 1092 (61.6%) were classified as presumed BRAF wild-type (BRAFwt). Immune checkpoint inhibitor (ICI)-based regimens were the most common first-line (1L) therapies (78.5%), while BRAF + MEK inhibitors accounted for 14.4%. In second-line (2L) therapy, sequencing patterns were diverse, with no dominant 2L pathway observed. BRAF + MEK inhibitors were the most frequently used 2L therapy (27.5%). In patients with BRAFmut, targeted therapy predominated in 2L (71.8%), whereas ICI-based regimens remained dominant in patients with BRAFwt (84.9%). 1L therapy was significantly associated with 2L treatment selection (p < 0.001). Treatment distributions differed across index years for both 1L (p = 0.001) and 2L (p = 0.005) therapies. Over time, use of PD-1 monotherapy decreased, while use of nivolumab plus ipilimumab increased; use of BRAF + MEK therapy remained stable.

Although treatment practices for advanced melanoma continue to evolve in response to emerging clinical evidence, substantial uncertainty remains regarding optimal treatment sequencing after 1L progression. These findings highlight the need for prospective sequencing studies and more effective therapeutic options following disease progression.