A Phase I Trial of Alpelisib Combined With Capecitabine in Patients With HER2-Negative Metastatic Breast Cancer.
Alpelisib
Breast cancer
Capecitabine
PI3K
PIK3CA
Journal
Clinical breast cancer
ISSN: 1938-0666
Titre abrégé: Clin Breast Cancer
Pays: United States
ID NLM: 100898731
Informations de publication
Date de publication:
08 Aug 2024
08 Aug 2024
Historique:
received:
02
04
2024
revised:
14
07
2024
accepted:
02
08
2024
medline:
1
9
2024
pubmed:
1
9
2024
entrez:
31
8
2024
Statut:
aheadofprint
Résumé
Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown. This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study.
Sections du résumé
BACKGROUND
BACKGROUND
Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown.
PATIENTS AND METHODS
METHODS
This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m
RESULTS
RESULTS
Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m
CONCLUSION
CONCLUSIONS
This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study.
Identifiants
pubmed: 39217059
pii: S1526-8209(24)00213-1
doi: 10.1016/j.clbc.2024.08.001
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure YA reports consulting income from Exact Sciences, AstraZeneca and Pfizer. C.K.A. reports research funding provided by PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, Astra Zeneca, Elucida, Caris, Incyclix; consulting for Genentech, Eisai, IPSEN, Seattle Genetics, Astra Zeneca, Novartis, Immunomedics, Elucida, Athenex, Roche; royalties from UpToDate, Jones and Bartlett. L.A.C. reports research funding from Genentech/Roche, AstraZeneca, Lilly, Novartis, Veracyte, Nanostring. C.M.P. is an equity stockholder and board of director member of BioClassifer LLC and is listed as inventor on patent applications for the Breast PAM50 assay. E.C.D. reports consulting income from Sanofi, research funding from Novartis, Genentech, Bayer, Pfizer, and Merck and a family member who received past consulting income from Novartis. L.A.C reports research funding from AstraZeneca, Genentech/Roche, Lilly, Merck, Nanostring, Novartis, SeaGen, and Veracyte. P.K.M. is a full-time employee and equity stockholder with Veracyte.