Capivasertib Combo Receives Approval in Japan for HR+/HER2– Breast Cancer

The FDA previously approved capivasertib plus fulvestrant for patients with previously treated, locally advanced or metastatic, HR–positive, HER2-negative breast cancer harboring at least 1 PIK3CA, AKT, or PTEN alteration in November 2023.

Capivasertib (Truqap) plus fulvestrant (Faslodex) has received approval as a treatment for adult patients with unresectable or recurrent hormone receptor (HR)–positive, HER2-negative breast cancer harboring PIK3CA, AKT1, or PTEN alterations after progression on prior endocrine therapy in Japan, according to a press release from developers AstraZeneca.¹

The Japanese Ministry of Health, Labour, and Welfare (MHLW) based its approval on findings from the phase 3 CAPItello-291 trial (NCT04305496) assessing capivasertib/fulvestrant vs placebo/fulvestrant in patients with advanced or metastatic HR-positive, HER2-low or HER2-negative breast cancer. According to data published in The New England Journal of Medicine, the median progression-free survival (PFS) was 7.3 months with capivasertib plus fulvestrant vs 3.1 months with placebo plus fulvestrant (HR, 0.50; 95% CI, 0.38-0.65; P <.001).²

Common grade 3 or higher adverse effects (AEs) in the capivasertib and placebo arms, respectively, included rash (12.1% vs 0.3%), diarrhea (9.3% vs 0.3%), and hyperglycemia (2.3% vs 0.3%). Additionally, 13.0% and 2.3% of patients from each respective arm discontinued study treatment due to AEs.

“The approval of capivasertib and fulvestrant signifies a new era of care in advanced [HR]-positive breast cancer in Japan, providing a much-needed new treatment option for approximately half of the patients in this setting who have tumors harboring mutations in PIK3CA, AKT1 or alterations in PTEN,” Masakazu Toi, MD, PhD, the director of Tokyo Metropolitan Cancer and Infectious Diseases Center at Komagome Hospital, Japan, said in the press release.¹ “It is important for us to detect these specific tumor biomarker alterations in each patient we see so that they are potentially able to benefit from this important combination to extend the effectiveness of endocrine-based treatment and delay disease progression.”

In the international CAPItello-291 trial, 708 patients were assigned 1:1 to receive capivasertib orally at 400 mg twice a day for 4 days followed by 3 days off or matched placebo plus fulvestrant at 500 mg intramuscularly every 2 weeks for the first 3 injections followed by every 4 weeks thereafter. The trial’s dual primary end points were PFS in the overall population and among those whose tumors have PI3K/AKT pathway alterations.

The FDA previously approved capivasertib plus fulvestrant for patients with previously treated, locally advanced or metastatic, HR–positive, HER2-negative breast cancer harboring at least 1 PIK3CA, AKT, or PTEN alteration in November 2023.³ Supporting data for this approval came from the CAPItello-291 trial.

References

1. Truqap plus Faslodex approved in Japan for patients with advanced HR-positive breast cancer. News release. AstraZeneca. March 27, 2024. Accessed March 28, 2024. https://tinyurl.com/3ps6pepp
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. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed March 28, 2024. https://tinyurl.com/4rc8w8xn