Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Biomarkers, Tumor
Breast Neoplasms
/ drug therapy
Cyclin-Dependent Kinase 4
/ antagonists & inhibitors
Cyclin-Dependent Kinase 6
/ antagonists & inhibitors
Female
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Letrozole
/ administration & dosage
Middle Aged
Piperazines
/ administration & dosage
Pyridines
/ administration & dosage
Receptors, Estrogen
/ analysis
CDK 4/6 inhibitor
Hormone receptor positive
Immune checkpoint inhibitor
Metastatic breast cancer
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
30
03
2021
revised:
11
05
2021
accepted:
24
05
2021
pubmed:
5
7
2021
medline:
18
11
2021
entrez:
4
7
2021
Statut:
ppublish
Résumé
CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumab and letrozole in women with hormone receptor positive (HR Women with stage IV HR Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33-70) and cohort 2 median age was 55 (37-75). Cohort 1 closed early due to limited accrual. Grade III-IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PR and 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survival was 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI 36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately. The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR
Sections du résumé
BACKGROUND
CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumab and letrozole in women with hormone receptor positive (HR
PATIENTS AND METHODS
Women with stage IV HR
RESULTS
Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33-70) and cohort 2 median age was 55 (37-75). Cohort 1 closed early due to limited accrual. Grade III-IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PR and 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survival was 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI 36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately.
CONCLUSION
The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR
Identifiants
pubmed: 34217908
pii: S0959-8049(21)00363-4
doi: 10.1016/j.ejca.2021.05.035
pmc: PMC8691850
mid: NIHMS1721455
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers, Tumor
0
Immune Checkpoint Inhibitors
0
Piperazines
0
Pyridines
0
Receptors, Estrogen
0
Letrozole
7LKK855W8I
pembrolizumab
DPT0O3T46P
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Cyclin-Dependent Kinase 6
EC 2.7.11.22
palbociclib
G9ZF61LE7G
Banques de données
ClinicalTrials.gov
['NCT02778685']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-20Subventions
Organisme : NCI NIH HHS
ID : K12 CA001727
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206911
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement Dr. Yuan has contracted research sponsored by Merck, Eisai, Novartis, Puma, Genentech, Celgene, and Pfizer; is a consultant for Puma, Pfizer, and Immunomedics; and is on the Speakers Bureau for Eisai, Genentech, AstraZeneca, Daiichi Sankyo, Pfizer, Merck, and Immunomedics. The other authors declare they have no competing interests.
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