Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma.
Eur J Cancer
; 144: 182-191, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-33360855
ABSTRACT
OBJECTIVE:
Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006. PATIENTS ANDMETHODS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Clinical Trials as Topic
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Drug-Related Side Effects and Adverse Reactions
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents, Immunological
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Melanoma
Type of study:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Systematic_reviews
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Eur J Cancer
Year:
2021
Document type:
Article