AstraZeneca Announces China Approval of Truqap (Capivasertib) in Combination with Fulvestrant for HR-Positive, HER2-Negative Advanced Breast Cancer with PIK3CA/AKT1/PTEN Alterations

China Finance and Economics News, April 22nd: AstraZeneca announced today that the National Medical Products Administration (NMPA) has officially approved Truqap (Quankotide, Capivasertib tablets) in combination with fulvestrant for adult patients with locally advanced or metastatic breast cancer that is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and accompanied by one or more PIK3CA/AKT1/PTEN alterations. The indication covers patients whose disease has progressed after receiving at least one endocrine therapy in the metastatic setting, or who have relapsed during adjuvant therapy or within 12 months after completing adjuvant therapy.

The approval in China is based on the positive results of the global Phase III CAPItello-291 study previously published in The New England Journal of Medicine. The positive results from the Chinese cohort, which were consistent with the global study findings and announced at the 2023 European Society for Medical Oncology Asia (ESMO Asia) Congress, also supported this approval.

In the global population of this trial, 69% of patients had previously received treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors. The study results showed that for patients with biomarker alterations in the PI3K/AKT pathway, capivasertib combined with fulvestrant reduced the risk of disease progression or death by 50% compared to fulvestrant alone (hazard ratio 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) was 7.3 months vs. 3.1 months). In the Chinese population, compared to fulvestrant alone, capivasertib combined with fulvestrant reduced the risk of disease progression or death by 59% in patients with alterations in the PIK3CA, AKT1, or PTEN genes (hazard ratio 0.41; median PFS was 5.7 months vs. 1.9 months).

Breast cancer is one of the most prevalent malignant tumors among women in China, with over 350,000 confirmed cases and approximately 75,000 patient deaths in 2022 alone. Globally, HR-positive breast cancer (expressing estrogen and/or progesterone receptors) is the most common breast cancer subtype, with 70% of breast cancers classified as HR-positive and HER2-negative. Endocrine therapy combined with cyclin-dependent kinase (CDK)4/6 inhibitors is widely used as the initial treatment for patients with advanced breast cancer. However, tumors often develop resistance to these therapies, especially when they harbor PIK3CA, AKT1, or PTEN alterations. Therefore, there is an urgent need for more combination regimens based on endocrine therapy to optimize the duration and efficacy of endocrine treatment benefits. Global data indicate that about 50% of patients with HR-positive advanced breast cancer carry alterations in the PIK3CA, AKT1, or PTEN genes. Among the Chinese population, approximately 57% of HR-positive, HER2-negative breast cancer patients have PIK3CA, AKT1, or PTEN alterations, with proportions as high as 8.4% carrying PTEN alterations and 7.7% with AKT1 alterations.

Professor Hu Xichun, Chief of the Department of Internal Medicine at Fudan University Shanghai Cancer Center, member of the ESMO International Breast Cancer Expert Committee, and the leading investigator in China for the CAPItello-291 trial, stated that patients with advanced HR-positive breast cancer often experience disease progression or resistance during first-line endocrine therapy. "We are very pleased to see that this approval brings a new treatment option for patients with advanced HR-positive breast cancer who have PIK3CA, AKT1, or PTEN gene alterations, which is expected to help delay disease progression and prolong survival time. This also highlights the importance of precision diagnosis and treatment in breast cancer."

Dr. He Jing, Senior Vice President of AstraZeneca Global and Head of Global R&D in China, stated: "Breast cancer poses a serious threat to the lives and health of women in China, and there is an urgent unmet need for innovative treatment options for patients. Capivasertib is the first and only AKT inhibitor approved in China for breast cancer patients with PIK3CA/AKT1/PTEN alterations. This approval fully demonstrates the innovative value of our drug. In the future, we will continue to leverage our R&D capabilities and pipeline to make every effort to overcome this deadly disease, breast cancer."

"Capivasertib has the potential to extend the benefits of currently widely used endocrine therapies and help delay disease progression in HR-positive advanced breast cancer patients. Its approval marks another significant milestone in AstraZeneca China's ongoing exploration in the field of breast cancer," said Guan Dongmei, General Manager of AstraZeneca China’s Oncology Business. AstraZeneca is aligned with the Healthy China 2030 cancer prevention and treatment goals, and looks forward to bringing more globally innovative oncology drugs to patients across China, contributing to the achievement of the grand goals of Healthy China 2030.

In the CAPItello-291 trial, the safety profile of capivasertib in combination with fulvestrant was generally consistent with findings from previous combination therapy trials. Based on the results of the CAPItello-291 trial, capivasertib has now been approved in the United States, the European Union, Japan, and other countries and regions for the treatment of patients with HR-positive advanced breast cancer.