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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.ejca.2020.11.010
Journal or Publication Title: European Journal of Cancer
Volume: 144
Page Range: pp. 182-191
Date: 2021
Divisions: Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.1016/j.ejca.2020.11.010
ISSN: 09598049
Date Deposited: 10 Jun 2021 06:10
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.

Keywords: Advanced melanoma; Corticosteroid use; Immune-checkpoint inhibitors; Immune-related adverse events; Immunomodulating drugs; PD-1 inhibitors; Pembrolizumab.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Creators:
Creators
Email
Robert, Caroline
UNSPECIFIED
Hwu, Wen-Jen
UNSPECIFIED
Hamid, Omid
UNSPECIFIED
Ribas, Antoni
UNSPECIFIED
Weber, Jeffrey S.
UNSPECIFIED
Daud, Adil I.
UNSPECIFIED
Hodi, F. Stephen
UNSPECIFIED
Wolchok, Jedd D.
UNSPECIFIED
Mitchell, Tara C.
UNSPECIFIED
Hersey, Peter
UNSPECIFIED
Dronca, Roxana
UNSPECIFIED
Joseph, Richard W.
UNSPECIFIED
Boutros, Celine
UNSPECIFIED
Min, Le
UNSPECIFIED
Long, Georgina V.
UNSPECIFIED
Schachter, Jacob
UNSPECIFIED
Puzanov, Igor
UNSPECIFIED
Dummer, Reinhard
UNSPECIFIED
Lin, Jianxin
UNSPECIFIED
Ibrahim, Nageatte
UNSPECIFIED
Diede, Scott J.
UNSPECIFIED
Carlino, Matteo S.
UNSPECIFIED
Joshua, Anthony M.
UNSPECIFIED
Last Modified: 10 Jun 2021 06:10
URI: https://eprints.centenary.org.au/id/eprint/1035

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