Abstract

Background: Boa_Image_Frame treatment for resected stage III melanomas typically involves a fixed dose of 200 mg of pembrolizumab every three weeks (Q3W). The FDA approved an alternate dosing of 400 mg every six weeks (Q6W), based on pharmacokinetic modelling, without conducting formal comparative studies. These modelling suggest that flat dosing schedules achieve comparable target engagement. The safety of the Q6W dosing has not been thoroughly investigated. There is a lack of direct comparison between the Q3W and Q6W regimens for completely resected Stage III melanoma. Objective: To compare the safety & efficacy of Q3W & Q6W schedules in a real-world clinical setting Methods: Retrospective study, conducted from 2019-2023, included patients with high-risk node-positive melanomas. Eligible participants were those with Stage III melanoma & lymph node involvement who had undergone complete resection and received at least one cycle of pembrolizumab. The study examined two dosing regimens: 200 mg Q3W & 400 mg Q6W. Pre-specified baseline characteristics & reported toxicities were analyzed. Systemic therapy details were retrospectively collected through the SVUH pharmacy database. Toxicities were graded according to the Common Terminology Criteria for Adverse Events. The primary outcomes were recurrence-free survival (RFS), & the occurrence and severity of immune-mediated adverse events (irAEs) across the dosing schedules. Results: A total of 60 consecutive patients with resected stage III malignant melanoma were treated with pembrolizumab between 2019-2023. 24 patients received a 200 mg dose Q3W, while 36 patients received a 400 mg dose Q6W. The median time to onset of irAEs was 103 days for Q3W & 128 days for Q6W (p = 0.34). Any-grade irAEs were observed in 70% of the Q3W group & 52.7% of the Q6W group. Grade ≥ 3 irAEs occurred in 19% of the Q3W group & 18% of the Q6W group. The estimated 12-month RFS was 72.1% for Q3W & 76.8% for Q6W (HR 0.93; 95%CI 0.50-1.73). Three-year RFS was 69.1% for Q3W & 68.9% for Q6W (HR 0.56, 99% CI 0.39-0.8). Conclusions: This real-life experience shows that Q6W regimen is safe & effective. Both Q3W & Q6W regimens offer comparable effectiveness, as evidenced by similar RFS rates at 12 months & 3 years. The incidence of irAEs was marginally lower in the Q6W group, but the difference was not statistically significant. The Q6W dosing schedule may reduce the burden on health service resources, providing significant time savings & potentially reducing financial toxicity