Association of Extended Dosing Intervals or Delays in Pembrolizumab-based Regimens With Survival Outcomes in Advanced Non-small-cell Lung Cancer.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Agents, Immunological
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cohort Studies
Drug Administration Schedule
Female
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Progression-Free Survival
Retrospective Studies
Survival Rate
Time Factors
Treatment Outcome
Extended-interval dosing
Immune-related adverse event
Patient-physician preference
Real-world outcomes
Treatment delays
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
12
02
2020
revised:
08
05
2020
accepted:
26
05
2020
pubmed:
13
7
2020
medline:
30
12
2021
entrez:
13
7
2020
Statut:
ppublish
Résumé
Besides modeling/simulation-based analysis, no post-approval studies have evaluated the optimal administration frequency of pembrolizumab in non-small-cell lung cancer (NSCLC). We performed a multicenter retrospective cohort study to evaluate the association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in patients with advanced NSCLC. Those who had received at least 4 cycles in routine practice were divided into 2 groups: nonstandard (Non-Std, ≥ 2 cycles at intervals > 3 weeks + 3 days) and standard (Std, all cycles every 3 weeks or 1 cycle > 3 weeks + 3 days). Among 150 patients, 92 (61%) were eligible for the study (Non-Std, 27; Std, 65). The reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs) (33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). The Non-Std group was more likely to have a higher programmed death-ligand 1 tumor proportion score, a higher number of treatment cycles, and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival and progression-free survival in the Non-Std group compared with the Std group. After multivariable adjustment for confounding factors, there was no significant difference in overall survival (hazard ratio, 1.2; 95% confidence interval, 0.3-4.8; P = .824) or progression-free survival (hazard ratio, 2.6; 95% confidence interval, 0.7-9.6; P = .157) between the 2 groups. Our study shows that a significant proportion of patients with advanced NSCLC receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials.
Sections du résumé
BACKGROUND
Besides modeling/simulation-based analysis, no post-approval studies have evaluated the optimal administration frequency of pembrolizumab in non-small-cell lung cancer (NSCLC).
PATIENTS AND METHODS
We performed a multicenter retrospective cohort study to evaluate the association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in patients with advanced NSCLC. Those who had received at least 4 cycles in routine practice were divided into 2 groups: nonstandard (Non-Std, ≥ 2 cycles at intervals > 3 weeks + 3 days) and standard (Std, all cycles every 3 weeks or 1 cycle > 3 weeks + 3 days).
RESULTS
Among 150 patients, 92 (61%) were eligible for the study (Non-Std, 27; Std, 65). The reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs) (33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). The Non-Std group was more likely to have a higher programmed death-ligand 1 tumor proportion score, a higher number of treatment cycles, and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival and progression-free survival in the Non-Std group compared with the Std group. After multivariable adjustment for confounding factors, there was no significant difference in overall survival (hazard ratio, 1.2; 95% confidence interval, 0.3-4.8; P = .824) or progression-free survival (hazard ratio, 2.6; 95% confidence interval, 0.7-9.6; P = .157) between the 2 groups.
CONCLUSION
Our study shows that a significant proportion of patients with advanced NSCLC receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials.
Identifiants
pubmed: 32653295
pii: S1525-7304(20)30168-6
doi: 10.1016/j.cllc.2020.05.028
pmc: PMC7273162
mid: NIHMS1601181
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
pembrolizumab
DPT0O3T46P
Types de publication
Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e379-e389Subventions
Organisme : NCI NIH HHS
ID : R37 CA218707
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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