Capivasertib and fulvestrant for patients with HR-positive/HER2-negative advanced breast cancer: analysis of the subgroup of patients from Japan in the phase 3 CAPItello-291 trial

Abstract

Background: In CAPItello-291, capivasertib-fulvestrant significantly improved progression-free survival (PFS) versus placebo-fulvestrant in the overall and PIK3CA/AKT1/PTEN-altered population with hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. Capivasertib-fulvestrant is approved in Japan for the treatment of patients with one or more tumor biomarker alterations (PIK3CA, AKT1 or PTEN). Here, we report outcomes in the CAPItello-291 subgroup of patients from Japan.

Methods: Adults with HR-positive/HER2-negative advanced breast cancer whose disease had relapsed or progressed during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy, were randomly assigned (1:1 ratio) to receive capivasertib or placebo, plus fulvestrant. The dual primary endpoint was investigator-assessed PFS in the overall and PIK3CA/AKT1/PTEN-altered population. Safety was a secondary endpoint.

Results: Of 708 patients randomized in CAPItello-291, 78 were from Japan (37 randomized to capivasertib-fulvestrant and 41 to placebo-fulvestrant). In the Japan subgroup, PFS numerically favored the capivasertib-fulvestrant arm (hazard ratio 0.73; 95% CI 0.40-1.28), consistent with the analysis of PFS in the global population. Similarly, in the Japan subgroup of patients with PIK3CA/AKT1/PTEN-altered tumors, PFS favored the capivasertib-fulvestrant arm (hazard ratio 0.65; 95% CI 0.29-1.39), consistent with the global population. The adverse event profile of capivasertib-fulvestrant in the Japan subgroup was broadly similar to that in the global population; no new safety concerns were identified.

Conclusion: Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen.

Keywords: AKT inhibitor; Capivasertib; Hormone receptor-positive breast cancer; Post-CDK4/6.

Fig. 1

Investigator-assessed PFS in a the Japan subgroup, and b the global CAPItello-291 population. The hazard ratio was estimated in the Japan subgroup using the Cox proportional hazards model stratified by previous CDK4/6 inhibitor use, and in the global CAPItello-291 population using the Cox proportional hazards model stratified according to the presence or absence of liver metastases, previous CDK4/6 inhibitor use, and geographic region. Tick marks indicate censored data. b From New England Journal of Medicine. Turner et al. [16]. Copyright © (2023) Massachusetts Medical Society. Reprinted with permission. CI confidence interval, PFS progression-free survival

Fig. 2

Investigator-assessed PFS in patients with PIK3CA/AKT1/PTEN-altered tumors in a the Japan subgroup, and b the global CAPItello-291 population. The hazard ratio was estimated in the Japan subgroup using an unstratified Cox proportional hazards model, and in the global CAPItello-291 population using the Cox proportional hazards model stratified according to the presence or absence of liver metastases and previous CDK4/6 inhibitor use. Tick marks indicate censored data. b New England Journal of Medicine. Turner et al. [16]. Copyright © (2023) Massachusetts Medical Society. Reprinted with permission. AKT1 Akt serine/threonine kinase 1, CI confidence interval, NC not calculable, PFS progression-free survival, PIK3CA catalytic subunit of phosphatidylinositol-3-kinase, PTEN phosphatase and tensin homolog