Durable Clinical Benefit in Patients with Advanced Cutaneous Melanoma after Discontinuation of Anti-PD-1 Therapies Due to Immune-Related Adverse Events.

Durable Clinical Benefit in Patients with Advanced Cutaneous Melanoma after Discontinuation of Anti-PD-1 Therapies Due to Immune-Related Adverse Events.

Publication date: Mar 04, 2019

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.

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).

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).

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.

Open Access PDF

Swami, U., , Monga, Bossler, A.D., Zakharia, Y., and Milhem, M. Durable Clinical Benefit in Patients with Advanced Cutaneous Melanoma after Discontinuation of Anti-PD-1 Therapies Due to Immune-Related Adverse Events. 24914. 2019 J Oncol (2019):

Concepts Keywords
Autoimmune Diseases Cancer immunotherapy
Hispanic Clinical endpoint
Holden Nivolumab
Iowa Pembrolizumab
Median Melanoma
Melanoma Bristol-Myers Squibb
Metastatic Breakthrough therapy
Toxicity Antineoplastic drugs
Cancer treatments
Clinical medicine
Medicine
Advanced melanoma
Melanoma Treatment

Semantics

Type Source Name
drug DRUGBANK Pembrolizumab
drug DRUGBANK Nivolumab
disease MESH melanoma
pathway KEGG Melanoma
disease MESH disease progression
disease MESH Cancer
disease MESH autoimmune diseases

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