Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma. (February 2021)

• Record Type: Journal Article
• Authors: Robert, Caroline; Hwu, Wen-Jen; Hamid, Omid; Ribas, Antoni; Weber, Jeffrey S.; Daud, Adil I.; Hodi, F. Stephen; Wolchok, Jedd D.; Mitchell, Tara C.; Hersey, Peter; Dronca, Roxana; Joseph, Richard W.; Boutros, Celine; Min, Le; Long, Georgina V.; Schachter, Jacob; Puzanov, Igor; Dummer, Reinhard; Lin, Jianxin; Ibrahim, Nageatte; Diede, Scott J.; Carlino, Matteo S.; Joshua, Anthony M.
• Is Part Of: European journal of cancer. Volume 144(2021)
• Page Start: 182
• Page End: 191
• Publication Date: 2021-02
• Subjects: Pembrolizumab -- Advanced melanoma -- Immune-related adverse events -- Immune-checkpoint inhibitors -- PD-1 inhibitors -- Immunomodulating drugs -- Corticosteroid use; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2020.11.010
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Objective: Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006. Patients and methods: Analysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147. Results: Adverse events (AEs) were analyzed for 1567 patients (median follow-up, 42.4 months). Most AEs were mild/moderate; grade 3/4 treatment-related AEs occurred in 17.7% of patients. Two pembrolizumab-related deaths occurred. Any-grade immune-mediated AEs (imAEs) occurred in 23.0%, most commonly hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); grade 3/4 imAEs occurred in 6.9% of patients. Most imAEs occurred within 16 weeks of treatment. In landmark analysis, patients who did ( n = 79) versus did not ( n = 384) develop imAEs had similar objective response rates (ORRs) (64.6% versus 63.0%); median time to response (TTR), 5.6 months for both; median duration of response (DOR), 20.0 versus 25.3 months; median progression-free survival (PFS), 17.0 versus 17.7 months; median overall survival (OS), not reached (NR) versus 43 months ( p = 0.1104). Patients who did ( n = 17) versus did not ( n = 62) receive systemic corticosteroids had similar ORRs (70.6% vs. 62.9%) and median TTR (6.4 vs. 5.6 months) but numerically shorter median PFS (9.9 vs. 17.0 months); median DOR, 14.2 months versus NR; median OS, NR for both. Conclusions: These results enhance the knowledge base for pembrolizumab in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAEs or systemic corticosteroid use. Clinical trial registry: NCT01295827, NCT01704287, NCT01866319. Highlights: Long-term (3.5 years) safety analysis of pembrolizumab monotherapy in melanoma. Data were pooled from KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006 trials ( N = 1567). Treatment-related AEs and immune-mediated AEs (imAE) were generally mild/moderate. In landmark analysis, efficacy was similar regardless of imAEs or corticosteroid use. With no new toxicity signals, results support pembrolizumab use in advanced melanoma.