Abstract
One year of adjuvant anti-PD-1 has improved disease-free survival in Stage III melanoma. It is unknown whether shorter treatment duration affects outcomes. Real-world data may help clarify this. In this retrospective observational study, patients with resected Stage III/IV melanoma receiving adjuvant anti-PD-1 in the Netherlands from 2018 to 2023 were included from the Dutch Melanoma Treatment Registry. Three cohorts were identified: completion of 12 months adjuvant anti-PD-1 (A), early discontinuation due to toxicity (B), early discontinuation for other reasons (C). To reduce immortal time bias, 12-month landmark analyses were performed. Recurrence-free survival (RFS) and overall survival (OS) were compared; multivariable Cox regression was performed. We included 1502 patients: 605 in cohort A, 332 in cohort B, 565 in cohort C. Two-year RFS was 85.6% (95% CI: 82.6-88.7), 76.3% (95% CI: 71.4-81.6) and 80.0% (95% CI: 76.4-83.7) in cohort A, B and C, respectively. The adjusted hazard ratio (adjHR) for recurrence and all-cause death was 1.37 (95% CI: 1.03-1.82) in cohort B vs. A and 1.22 (95% CI: 0.95-1.56) in cohort C versus A. Two-year OS was 98.2% (95% CI: 97.0-99.4), 94.6% (95% CI: 91.9-97.4) and 96.7% (95% CI: 95.0-98.3) in cohort A, B and C. The adjHR of all-cause death was 1.82 (95% CI: 1.20-2.75) in cohort B versus A and 1.30 (95% CI: 0.89-1.89) in cohort C versus A. Early discontinuation of anti-PD-1 due to toxicity was associated with worse RFS and OS compared to completing treatment, which was not observed for early discontinuation for other reasons. These findings support prospective evaluation of adjuvant therapy duration in melanoma.