Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial.
Aged
Cetuximab
/ administration & dosage
Cyclin D1
/ genetics
Cyclin-Dependent Kinase 4
/ antagonists & inhibitors
Cyclin-Dependent Kinase 6
/ antagonists & inhibitors
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Disease-Free Survival
Drug Resistance, Neoplasm
/ drug effects
Female
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Papillomaviridae
/ pathogenicity
Piperazines
/ administration & dosage
Platinum
/ administration & dosage
Pyridines
/ administration & dosage
Squamous Cell Carcinoma of Head and Neck
/ drug therapy
Treatment Outcome
Journal
The Lancet. Oncology
ISSN: 1474-5488
Titre abrégé: Lancet Oncol
Pays: England
ID NLM: 100957246
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
05
03
2019
revised:
14
05
2019
accepted:
28
05
2019
pubmed:
29
7
2019
medline:
1
7
2020
entrez:
29
7
2019
Statut:
ppublish
Résumé
Most head and neck squamous-cell carcinomas (HNSCCs) are driven by p16 We did a multicentre, multigroup, phase 2 trial to evaluate the activity of palbociclib and cetuximab in platinum-resistant (group 1) and cetuximab-resistant (group 2) HPV-unrelated HNSCC. The study was done across eight university sites in the USA. Eligibility required measurable disease (according to Response Evaluation Criteria in Solid Tumors, version 1·1 [RECIST 1·1]), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, age of 18 years or older, and disease progression on platinum but cetuximab-naive (group 1) or disease progression on cetuximab (group 2). All patients received palbociclib orally (125 mg/day, on days 1-21) and intravenous cetuximab (400 mg/m Between Oct 19, 2015, and Nov 7, 2018, 62 patients were enrolled onto the trial: 30 patients were enrolled in group 1 and 32 in group 2. Median follow-up was 5·4 months (IQR 4·4-12·1) for group 1 and 5·5 months (4·3-8·3) for group 2. In group 1, of 28 evaluable patients, an objective response was achieved by 11 (39%; 95% CI 22-59). In group 2, of 27 evaluable patients, an objective response was achieved by five (19%; 6-38) in group 2. The most common grade 3-4 palbociclib-related adverse event was neutropenia (in 21 [34%] of 62 patients). No treatment-related deaths occurred. In patients with platinum-resistant or cetuximab-resistant HPV-unrelated HNSCC, palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated HNSCC. Pfizer.
Sections du résumé
BACKGROUND
Most head and neck squamous-cell carcinomas (HNSCCs) are driven by p16
METHODS
We did a multicentre, multigroup, phase 2 trial to evaluate the activity of palbociclib and cetuximab in platinum-resistant (group 1) and cetuximab-resistant (group 2) HPV-unrelated HNSCC. The study was done across eight university sites in the USA. Eligibility required measurable disease (according to Response Evaluation Criteria in Solid Tumors, version 1·1 [RECIST 1·1]), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, age of 18 years or older, and disease progression on platinum but cetuximab-naive (group 1) or disease progression on cetuximab (group 2). All patients received palbociclib orally (125 mg/day, on days 1-21) and intravenous cetuximab (400 mg/m
FINDINGS
Between Oct 19, 2015, and Nov 7, 2018, 62 patients were enrolled onto the trial: 30 patients were enrolled in group 1 and 32 in group 2. Median follow-up was 5·4 months (IQR 4·4-12·1) for group 1 and 5·5 months (4·3-8·3) for group 2. In group 1, of 28 evaluable patients, an objective response was achieved by 11 (39%; 95% CI 22-59). In group 2, of 27 evaluable patients, an objective response was achieved by five (19%; 6-38) in group 2. The most common grade 3-4 palbociclib-related adverse event was neutropenia (in 21 [34%] of 62 patients). No treatment-related deaths occurred.
INTERPRETATION
In patients with platinum-resistant or cetuximab-resistant HPV-unrelated HNSCC, palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated HNSCC.
FUNDING
Pfizer.
Identifiants
pubmed: 31351869
pii: S1470-2045(19)30405-X
doi: 10.1016/S1470-2045(19)30405-X
pii:
doi:
Substances chimiques
CCND1 protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Piperazines
0
Pyridines
0
Cyclin D1
136601-57-5
Platinum
49DFR088MY
CDK4 protein, human
EC 2.7.11.22
CDK6 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Cyclin-Dependent Kinase 6
EC 2.7.11.22
palbociclib
G9ZF61LE7G
Cetuximab
PQX0D8J21J
Banques de données
ClinicalTrials.gov
['NCT02101034']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1295-1305Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.