Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Department of Gynecology and Obstetrics
- Royal Marsden NHS Foundation Trust
- Autonomous University of Barcelona
- The Christie NHS Foundation Trust
- Institut Claudius Regaud
- Pangaea Oncology
- Universidad Europea de Madrid
- Universidad Ricardo Palma
- Fudan University
- Cornell University
- GBG Forschungs GmbH
- Agaplesion Bethanien Hospital
- Institute for Research in Biomedicine
- Icon Cancer Centre
- Sungkyunkwan University (SKKU)
- Yonsei University
- Kyoto University
- National Hospital Organization Kyushu Cancer Center
- Emek Medical Center
- GBUZ Moscow Clinical Scientific Center named after Loginov MHD
- AstraZeneca
- University of California at San Francisco
Abstract
BACKGROUND: AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited.
METHODS: In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed.
RESULTS: Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo.
CONCLUSIONS: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.).
Details
Original language | English |
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Pages (from-to) | 2058-2070 |
Number of pages | 13 |
Journal | The New England journal of medicine |
Volume | 388 |
Issue number | 22 |
Early online date | 31 May 2023 |
Publication status | Published - Jun 2023 |
Peer-reviewed | Yes |
External IDs
Scopus | 85160755629 |
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Mendeley | bfbfbd62-e2e0-3f21-816b-cfe80d0381d1 |
Keywords
Sustainable Development Goals
Keywords
- Female, Humans, Male, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Aromatase Inhibitors/adverse effects, Breast Neoplasms/drug therapy, Double-Blind Method, Fulvestrant/adverse effects, Neoplasm Recurrence, Local/drug therapy, Proto-Oncogene Proteins c-akt, Receptor, ErbB-2