Capivasertib in hormone receptor-positive advanced breast cancer Journal Article


Authors: Turner, N. C.; Oliveira, M.; Howell, S. J.; Dalenc, F.; Cortes, J.; Gomez Moreno, H. L.; Hu, X.; Jhaveri, K.; Krivorotko, P.; Loibl, S.; Morales Murillo, S.; Okera, M.; Park, Y. H.; Sohn, J.; Toi, M.; Tokunaga, E.; Yousef, S.; Zhukova, L.; de Bruin, E. C.; Grinsted, L.; Schiavon, G.; Foxley, A.; Rugo, H. S.; for the CAPItello-291 Study Group
Article Title: Capivasertib in hormone receptor-positive advanced breast cancer
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.). Copyright © 2023 Massachusetts Medical Society.
Keywords: protein kinase b; controlled study; antineoplastic agent; neoplasm recurrence, local; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; aromatase inhibitor; pathology; breast neoplasms; tumor recurrence; breast tumor; proto-oncogene proteins c-akt; receptor, erbb-2; drug therapy; double blind procedure; double-blind method; aromatase inhibitors; fulvestrant; humans; human; male; female; capivasertib
Journal Title: New England Journal of Medicine
Volume: 388
Issue: 22
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2023-06-01
Start Page: 2058
End Page: 2070
Language: English
DOI: 10.1056/NEJMoa2214131
PUBMED: 37256976
PROVIDER: scopus
PMCID: PMC11335038
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus
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  1. Komal Lachhman Jhaveri
    202 Jhaveri