Long-Term Follow-Up of Real-World Adjuvant Anti-PD-1 Checkpoint Inhibition and Targeted Therapy in Patients With Stage III Melanoma

Abstract

Purpose: Adjuvant treatment with immune checkpoint inhibition (PD-1) and targeted therapy (TT) with BRAF + MEK inhibitors significantly improved recurrence-free survival (RFS) of patients with stage III melanoma. We investigated efficacy of adjuvant therapy with PD-1 or TT under real-world conditions.

Materials and methods: A total of 589 patients with stage III melanoma who started adjuvant PD-1 or TT between June 2018 and September 2019 from 11 major German Dermatologic Cooperative Oncology Group skin cancer centers were followed for 4 years. End points were RFS, overall survival (OS), and melanoma-specific survival. Survival analyses and adjusted hazard ratios (HRs) were estimated with Kaplan-Meier and Cox proportional hazards model, inverse probability treatment weighting, and propensity score matching.

Results: RFS at 48 months was 42.9% (95% CI, 38.5 to 47.8) for all PD-1 patients and 52.6% (95% CI, 43.6 to 63.3) for TT patients. Among patients with BRAF mutation, rate of recurrence was higher for PD-1 compared with TT (HR, 1.57 [95% CI, 1.09 to 2.26]). OS at 4 years was 80.8% (95% CI, 73.6 to 88.7) for PD-1-treated patients with BRAF mutation and 87.3% (95% CI, 81.0 to 94.0) for TT patients. Patients starting adjuvant PD-1 after resection of macroscopic lymph node metastases had a higher risk of rapid recurrence (1-year RFS all PD-1 58%) compared with 87% in TT patients. Rate of recurrence after premature discontinuation (≤6 v >6 months treatment) was higher in TT patients (HR, 1.47 [95% CI, 0.67 to 3.23]), but not in PD-1 patients (HR, 1.07 [95% CI, 0.73 to 1.55]).

Conclusion: PD-1-treated patients with BRAF mutation had a markedly higher rate of relapse compared with TT patients. Rapid recurrences occurred particularly in PD-1-treated patients with previous macroscopic lymph node metastasis. Treatment duration shorter than 6 months did not negatively affect RFS in PD-1, but in TT patients.