Long-term follow-up of real-world adjuvant anti-PD1 checkpoint inhibition and targeted therapy in stage III melanoma patients.

Purpose: Adjuvant treatment with immune checkpoint inhibition (PD1) and targeted therapy (TT) with BRAF+MEK inhibitors significantly improved recurrence-free survival (RFS) of stage III melanoma patients. We investigated efficacy of adjuvant therapy with PD1 or TT under real-world conditions.

Patients and methods: A total of 589 stage III melanoma patients who started adjuvant PD1 or TT between June 2018 and September 2019 from 11 major German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer centers were followed for 4 years. Endpoints were RFS, overall (OS) and melanoma-specific survival (MSS). 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 38.5-47.8) for all PD1 patients and 52.6% (95% CI 43.6-63.3) for TT patients. Among BRAF-mutated patients, rate of recurrence was higher for PD1 compared to TT (HR 1.57, 95% CI 1.09-2.26). OS at 4 years was 80.8% [95%CI 73.6-88.7] for BRAF-mutated PD1 patients and 87.3% [95%CI 81.0-94.0]) for TT patients. Patients starting adjuvant PD1 after resection of macroscopic lymph node metastases had a higher risk of rapid recurrence (1-year RFS all PD1 58%) compared to 87% in TT patients. Rate of recurrence after premature discontinuation (≤6 vs. >6 months treatment) was higher in TT patients (HR 1.47, 95% CI 0.67-3.23), but not in PD1 patients (HR 1.07, 95% CI 0.73-1.55).

Conclusion: BRAF-mutated PD1 patients had a markedly higher rate of relapse compared to TT patients. Rapid recurrences occured particulary in PD1-treated patients with prior macroscopic lymph node metastasis. Treatment duration shorter than 6 months did not negatively impact RFS in PD1, but in TT patients.