FDA Approves Truqap Plus Faslodex for Advanced HR-Positive Breast Cancer

The FDA has approved AstraZeneca’s capivasertib (Truqap) plus fulvestrant (Faslodex) for adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1 or PTEN biomarker alterations. As part of the regulatory action, the FDA also approved a companion diagnostic test to detect the PIK3CA, AKT1, and PTEN alterations.¹

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“Patients with advanced HR-positive breast cancer typically experience tumor progression or resistance with widely used first-line endocrine therapies and there is an urgent need to extend the effectiveness of these approaches,” said Komal Jhaveri, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, in a press release.¹ “The combination of capivasertib and fulvestrant, a first-of-its-kind combination, provides a much-needed new treatment option for up to half of patients in this setting with these specific biomarkers, offering the potential to delay disease progression and provide more time with their disease under control.”

The approval was based on findings from the Phase 3 CAPItello-291 trial (NCT4305496), in which the combination significantly improved progression-free survival (PFS) in patients with HR-positive, HER2-negative advanced breast cancer.²

In CAPItello-291, patients administered the combination showed a 40% reduced risk of progression. Patients administered Truqap plus Faslodex also achieved a clinically meaningful and statistically significant median PFS of 7.2 months compared with 3.6 months in those treated with a placebo plus Faslodex. The objective response rate (ORR) was 22.9% among patients administered Truqap plus Faslodex compared with 12.2% for those treated with a placebo plus Faslodex.

Among the patient population, 41% assigned to treatment had tumors with AKT pathway mutations. Patients administered Truqap plus Faslodex had a median PFS of 7.3 months and an ORR of 28.8% compared with 3.1 months and 9.7%, respectively, among those administered placebo plus Faslodex.

The most common adverse events (AEs) of grade 3 or higher among patients treated with Truqap plus Faslodex in CAPItello-291 trial were rashes, diarrhea, and hyperglycemia. The rate of discontinuation because of AEs was 13% among patients administered Truqap plus Faslodex compared with 2.3% among those administered placebo plus Faslodex.

HR-positive breast cancer is the most common subtype of the disease, as more than 65% of tumors are considered HR-positive and HER2-low or HER2-negative. Many HR-positive/HER2-negative breast cancers carry genetic mutations in AKT pathway genes, which promote tumor growth and may lead to endocrine resistance, affecting up to 50% of patients with advanced HR-positive breast cancer.¹ Although endocrine therapies are typically used to treat the disease, many patients develop resistance to first-line cyclin-dependent kinase 4/6 inhibitors and estrogen receptor-targeting treatments, which emphasizes the need for superior endocrine therapy-based options.

“The rapid US approval of Truqap reinforces the important role of the PI3K/AKT/PTEN pathway in HR-positive breast cancer and the critical need to test patients at the time of diagnosis, as up to 50% have tumors with these alterations,” said Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, in a press release. “As a first-in-class medicine, this approval provides a critical new option for patients in the US with this specific type of disease and we look forward to bringing Truqap to the many breast cancer patients who can benefit across the globe.”

References

1. TRUQAP (capivasertib) plus fulvestrant approved in the US for patients with advanced HR-positive breast cancer. AstraZeneca. News release. November 17, 2023. https://www.astrazeneca-us.com/media/press-releases/2023/truqap-capivasertib-plus-fulvestrant-approved-in-the-us-for-patients-with-advanced-hr-positive-breast-cancer-11172023.html

2. Adding capivasertib to fulvestrant improves progression-free survival in patients with advanced hormone receptor-positive breast cancer. News release. December 8, 2022. Accessed November 17, 2023. https://www.aacr.org/about-the-aacr/newsroom/news-releases/adding-capivasertib-to-fulvestrant-improves-progression-free-survival-in-patients-with-advanced-hormone-receptor-positive-breast-cancer/