Clinical News

Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) advanced breast cancer: Results from the Phase III CAPItello-291 trial

2023-01-16 

Abstract: The Phase III CAPItello-291 trial demonstrated statistically significant results of capivasertib plus fulvestrant in overall and the AKT pathway-altered HR+/HER2- advanced breast cancer

CDK4/6 inhibitors and endocrine therapies played important roles in HR+/HER2- advanced breast cancer, however, many patients would develop resistance to these therapies. AKT pathway consists of three main components, PIK3CA, AKT1, and PTEN, and pathway activation is postulated as one of the bypass mechanisms to endocrine therapies. Capivasertib, a selective inhibitor of AKT1/2/3, combined with fulvestrant has demonstrated improved PFS and OS in the phase II FAKTION trial for aromatase inhibitor-resistant, HR+/HER2- advanced breast cancer. CAPItello-291 is a phase III, randomized, double-blinded, placebo-controlled study to further investigate the efficacy of capivasertib plus fulvestrant. Of note, patients previously treated with CDK4/6 inhibitors are around 70% of the CAPItello-291 participants compared with 0% in FAKTION trial.

The mPFS was 7.2 vs. 3.6 months (adjusted HR: 0.60, p < 0.001), and the ORR was 22.9% vs. 12.2% in the overall population treated with capivasertib and fulvestrant combination vs. fulvestrant respectively. In the AKT pathway-altered cohort, the mPFS was 7.3 vs. 3.1 months (adjusted HR: 0.50, p < 0.001), and the ORR was 28.8% vs. 9.7%. The OS was not mature in both cohorts. According to the current analysis, prior use of CDK4/6 inhibitors did not affect the efficacy of capivasertib plus fulvestrant. The safety profiles are comparable in both the overall and AKT pathway-altered cohorts. The most common adverse events are diarrhea (72.4%), nausea (34.6%), rash (22.0%), fatigue (20.8%), and vomiting (20.6%). In summary, capivasertib and fulvestrant combination is a promising treatment option for HR+/HER2- advanced breast cancer patients progressed on the endocrine-based therapies.
 

Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the Phase III CAPItello-291 trial (Slide presentation in San Antonio Breast Cancer Symposium®, December 6–10, 2022)

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. (Lancet Oncol. 2022 Jul;23(7):851-864.)