European Commission Approves Capivasertib Plus Fulvestrant for ER+ Breast Cancer

Capivasertib (Truqap) plus fulvestrant (Faslodex) has received approval in the European Union (EU) for the treatment of adult patients with estrogen receptor (ER)-positive, HER2‑negative locally advanced or metastatic breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations following progression or recurrence on or after an endocrine-based regimen.¹

This regulatory decision was supported by findings from the phase 3 CAPItello-291 trial (NCT04305496), in which the combination elicited a median progression-free survival (PFS) of 7.3 months vs 3.1 months with placebo plus fulvestrant in patients with AKT pathway alterations (n = 289), translating to a 50% reduction in the risk of disease progression or death (HR, 0.50; 95% CI, 0.38-0.65; P ≤ .001).^1,2

Previously, in April 2024, the European Medicines Agency's Committee for Medicinal Products for Human Use recommended the combination for approval in this indication based on the CAPItello-291 findings.³

“Patients with advanced ER-positive breast cancer typically experience tumor progression or resistance with widely used endocrine-based treatment regimens, and there is an urgent need to provide them more time with their disease under control,” Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital and a senior clinical investigator of the Vall d’Hebron Institute of Oncology’s Breast Cancer Group in Barcelona, Spain, said in a news release.¹ “Today’s approval is welcome news for approximately half of [patients with] ER-positive breast cancer in Europe who have tumors with these biomarkers, and it is important for clinicians to test and identify eligible patients who may be able to benefit from this combination.”

“[Capivasertib] is now the first and only AKT inhibitor approved in the EU for patients with ER-positive breast cancer who have tumors harboring these specific biomarkers,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, added in the news release. “Breast cancer continues to be the leading cause of cancer-related death in Europe, and today’s news represents a significant step forward in providing an important new treatment option for patients in need of new, innovative therapies.”

In the overall CAPItello-291 population, the investigator-assessed median PFS was 7.2 months with capivasertib plus fulvestrant vs 3.6 months with placebo plus fulvestrant (HR, 0.60; 95% CI, 0.51-0.71; P < .001).²

In the overall population, the estimated 18-month overall survival (OS) rate in the capivasertib arm was 73.9% (95% CI, 68.3%-78.7%) vs 65.0% (95% CI, 58.7%-70.6%) in the placebo arm (HR, 0.74; 95% CI, 0.56-0.98). In the AKT pathway–altered population, the estimated 18-month OS rates were 73.2% (95% CI, 64.8%-80.0%) and 62.9% (95% CI, 53.1%-71.2%) in the capivasertib and placebo arms, respectively (HR, 0.69; 95% CI, 0.45 to 1.05).

In CAPItello-291, the safety profile of capivasertib plus fulvestrant was similar to that seen in previous trials investigating the combination.¹ The most frequently observed adverse effects (AEs) of grade 3 or higher in the capivasertib arm were rash (12.1%) and diarrhea (9.3%).² Moreover, 13.0% of patients in the capivasertib arm had AEs leading to treatment discontinuation vs 2.3% of those in the placebo arm.

In November 2023, the FDA approved capivasertib plus fulvestrant for the treatment of adult patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer with at least 1 PIK3CA, AKT1, or PTEN alteration, as detected by an FDA-approved test, after progression on 1 or more endocrine-based regimens in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.⁴

The combination is also approved for this indication in Japan, and regulatory applications for the regimen are under review in China and other countries.¹

References

1. Truqap plus Faslodex approved in the EU for patients with advanced ER-positive breast cancer. News release. AstraZeneca. June 20, 2024. Accessed June 20, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/truqap-plus-faslodex-approved-in-the-eu-for-patients-with-advanced-er-positive-breast-cancer.html
2. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor–positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070. doi:10.1056/NEJMoa2214131
3. Truqap plus Faslodex recommended for approval in the EU by CHMP for patients with advanced ER-positive breast cancer. News release. AstraZeneca. April 29, 2024. Accessed June 20, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/truqap-recommended-for-eu-breast-cancer-approval.html
4. FDA approves capivasertib with fulvestrant for breast cancer. FDA. November 16, 2023. Accessed June 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer