Abstract
Introduction Anti-PD-1 therapies, pembrolizumab and nivolumab, are currently the standard of care for treatment of patients with metastatic melanoma. Treatment is usually continued until toxicity or disease progression. Though these therapies are well tolerated, some patients discontinue them due to immune-related adverse events (irAE). Discontinuation of therapy brings challenges to their management due to limited treatment options and lack of long-term prognostic information for these patients. Herein, we reviewed patients at our institution to analyze their clinical outcomes. Materials and Methods Charts of 1264 consecutive patients enrolled between 8/1/2012 and 7/31/2017 at Melanoma Skin & Ocular Tissue Repositories at Holden Comprehensive Cancer Center at the University of Iowa Hospitals and Clinic were reviewed. Eligible patients were those who received single-agent anti-PD-1 therapy and subsequently discontinued it due to irAE. Reviewed data included patient demographics, prior medical history, baseline disease parameters, and outcomes. Kaplan-Meier survival analysis was done to determine progression-free survival (PFS) and overall survival (OS). Results Overall 169 patients with advanced, unresectable, or metastatic cutaneous melanoma received anti-PD-1 therapy of which 16 (9.5%) white, non-Hispanic patients with median age of 64.5 (range 35 to 81 years) discontinued treatment due to irAE. Fifteen patients received pembrolizumab and one received nivolumab. The median duration of treatment was 4.7 (range 0.7 to 11.5) months. Median follow-up was 30.3 (range 4.6 to 49.4) months. Median PFS was 24.6 months and median OS was not reached. Durable clinical benefit (time to progression or next treatment of more than 6 months from last treatment) was observed in 13 (81.2%) patients. At the time of analysis, 8 patients had progressed and 4 patients died (all-cause). Discussion Our results suggest that advanced melanoma patients discontinuing anti-PD-1 therapy due to irAE usually experience durable clinical benefit. However, caution is needed with these agents in patients with underlying autoimmune diseases.
Highlights
Anti-Programmed cell death 1 protein progression-free survival (PFS) (PD-1) therapies, pembrolizumab and nivolumab, are currently the standard of care for treatment of patients with metastatic melanoma
The median overall survival of metastatic melanoma has improved from 6 months to more than 3 years [2,3,4]
Two monoclonal antibodies targeted against Programmed cell death 1 protein PFS (PD-1) have been approved as first-line agents for the treatment of metastatic melanoma [1]
Summary
Monoclonal antibodies targeting programmed cell death 1 protein (PD-1) have shown to improve progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma [1]. The advent of anti-PD-1 antibodies along with antibodies targeting cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) and therapies targeting BRAF mutation has provided multiple options to treat patients with metastatic melanoma. Treatment discontinuation due to Journal of Oncology immune-related adverse events (irAEs) is estimated to occur in 15% to 25% of patients [3, 4] These patients lack effective therapies as many of them do not have actionable mutation, and even in patients with BRAF mutation, the median PFS with BRAF-MEK inhibitors is low (11 to 15 months) with a high rate of toxicities [1, 6, 7]. There is a need to understand the long-term prognosis of patients who undergo treatment discontinuation due to irAE to guide management decisions
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