(BRIEF) AstraZeneca announces the approval of Truqap (capivasertib) in combination with Faslodex (fulvestrant) through Japan’s Ministry of Health, Labor and Welfare (MHLW) for the treatment of unresectable or recurrent hormone receptor-positive, HER2-negative adult breast cancer patients. The approval, based on the positive effects of the phase III CAPItello-291 trial, marks a significant advance in breast cancer care in Japan, offering a new treatment option for patients with expressed biomarker alterations. The trial demonstrated a 50% relief in the threat of disease progression or death with the combination drug compared to Faslodex alone. The approval also includes an additional diagnostic test to identify applicable changes. Astex Therapeutics is expected to get invoices and royalties from AstraZeneca following the drug’s advertising sale in Japan.
(PRESS RELEASE) CAMBRIDGE, March 27, 2024 — /EuropaWire/ — AstraZeneca’s Truqap (capivasertib) in mixture with Faslodex (fulvestrant) has been approved in Japan for the treatment of adult patients with unresectable or recurrent hormone receptor (HR)-positive and HER2-negative hormone receptor (HR) breast cancer after progression after endocrine cure.
The approval from Japan’s Ministry of Health, Labor and Welfare (MHLW) was based on the effects of the phase III CAPItello-291 trial published in The New England Journal of Medicine. 1 In the trial, Truqap in combination with Faslodex reduced the threat of disease progression. or death up to 50% compared with Faslodex alone in patients with tumors with alterations in PI3K/AKT pathway biomarkers (based on a hazard ratio of 0. 50, 95% confidence period 0. 38-0. 65; P = <0. 001; median progression-free survival (PFS) 7. 3 vs. 3. 1 months). 1
In Japan, more than 90,000 women were diagnosed with breast cancer in 2022, and more than 17,000 patients died from the disease in the same year. 2 Globally, HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the highest subtype of non-unusual breast cancer, with more than 65% of tumors considered HR positive and HER2 low or HER2 negative. 3 Together, mutations in PIK3CA, AKT1, and PTEN alterations occur frequently and affect approximately 50% of patients. with complex RH-positive breast cancer. 4-6 Endocrine therapies are widely used in this setting, in combination with cyclin-dependent kinase (CDK) inhibitors,4/6 however, some tumors increase resistance to these treatments, highlighting the need for further combination. endocrine-treated approaches to prolong the time to start chemotherapy treatment. 7
Masakazu Toi, MD, PHD, Director of the Tokyo Metropolitan Center for Cancer and Infectious Diseases, Komagome Hospital, Japan, said, “The approval of capivasertib and fulvestrant marks a new era of care in hormone receptor-positive breast cancer in Japan, offering a new remedy option was needed for approximately a portion of patients in this setting who have tumors harboring PIK3CA mutations, AKT1 or PTEN alterations. It is vital for us to find those alterations expressed in tumor biomarkers in each and every patient we see, so they can potentially gain advantages from this vital combination to increase the efficacy of endocrine treatment and slow the progression of the disease.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Breast cancer is the most common cancer among women in Japan, and innovative new treatment functions are urgently needed. Today’s approval of Truqap, the first-in-class AKT inhibitor, represents a significant breakthrough for the treatment of HR-positive breast cancer and a vital new option for approximately fifty percent of patients who have tumors with those mutations or express alterations.
In the CAPItello-291 trial, the protection profile of Truqap plus Faslodex was similar to that observed in previous trials comparing this combination. 1
The MHLW has also approved other important diagnostics to detect applicable abnormalities (PIK3CA, AKT1 and PTEN).
Regulatory programs in China, the European Union, and several other countries are being reviewed lately, and this indication for Truqap in combination with Faslodex is already approved in the U. S. The effects of the CAPItello-291 trial have been reported in the U. S. and several other countries.
Remarks
HR-positive breast cancer (expressing estrogen or progesterone receptors, or both) is the most common subtype of breast cancer, with more than 65% of tumors HR-positive and HER2-low or HER2-negative. 3
The expansion of HR-positive breast cancer cells is driven through estrogen receptors (ERs), and endocrine cures that target ER-induced diseases are widely used as first-line cures in complex settings and are combined with CDK4/6 inhibitors. 7, 9,10 However, resistance to CDK4/6 inhibitors and endocrine cures develops in many patients with complex diseases Once this happens, treatment features are limited (chemocure is the current popular treatment) and survival rates are low, around 30%. of patients plan to live more than five years after diagnosis. 3, 9,11
Optimizing hormone treatment and combating resistance to allow patients to continue to benefit from those treatments, as well as identifying new treatments for those who are less likely to benefit from them, are active spaces in breast cancer research.
The overall trial enrolled 708 adult patients with histologically positive, low HER2, or negative breast cancer whose disease relapsed or progressed or after aromatase inhibitor therapy, with or without CDK4/6 inhibitor, and up to one line of chemotherapy. . The trial has a double number one endpoint of PFS in the general patient population and in a patient population with tumors with permissible alterations in the PI3K/AKT pathway (PIK3CA, AKT1, or PTEN genes). In the trial, about 40% of the tumors had these alterations and about 70% of the patients had taken a CDK4/6 inhibitor in the past.
Truqap in combination with Faslodex is approved in the U. S. The U. S. , Japan, and several other countries have been used to treat adult patients with HR-positive, HER2-negative locally complex or metastatic breast cancer with one or more well-founded biomarker alterations (PIK3CA, AKT1, or PTEN). Eligible patients will have progressed with at least one endocrine-based regimen in a metastatic setting or have experienced recurrence or within 12 months of the final touch of adjuvant therapy.
Truqap is recently being evaluated in phase III trials for the treatment of several subtypes of breast cancer and other tumor types, in combination with established therapies. The ongoing clinical trial program focuses on tumors that depend on signaling via the PI3K/AKT pathway, as well as tumors with biomarker alterations in this pathway.
Truqap discovered this through AstraZeneca following a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).
In the U. S. , the European Union, and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with metastatic breast cancer or HER2-negative or HR-positive complex whose cancer has progressed after endocrine therapy. Faslodex represents a hormone treatment technique that helps slow the expansion of the tumor by blocking and degrading the estrogen receptor, which is key in the progression of the disease.
Faslodex is approved as monotherapy or in combination with drugs from various drug classes, adding CDK4/6, PI3K, and AKT inhibitors, for the treatment of patients with HR-positive complex breast cancer and is being evaluated in combination with drugs from other classes of drugs.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in progression that leverage other mechanisms of action to address the biologically varied environment of breast cancer tumors.
Using Enhertu (trastuzumab deruxtecan), an antibody-drug conjugate (ADC) directed against HER2, AstraZeneca and Daiichi Sankyo aim to achieve results in previously treated HER2-positive and HER2-weak metastatic breast cancers and explore their possibilities in past lines of treatment. therapy. and in new contexts of breast cancer.
In HR-positive breast cancer, AstraZeneca continues to deliver results with the foundational drugs Faslodex and Zoladex (goserelin) and aims to remodel the HR-positive area with the first AKT inhibitor, Truqap, next-generation SERD, and potential new drugs. Camizestrant. AstraZeneca is also engaging with Daiichi Sankyo to explore the prospects of the TROP2-led ADC, datopotamab deruxtecan, in this context.
The PARP inhibitor Lynparza (olaparib) is a targeted therapy that has been studied in patients with early metastatic breast cancer with an inherited BRCA mutation. AstraZeneca and MSD (Merck
To provide much-needed treatment functions for patients with triple-negative breast cancer, a competitive form of breast cancer, AstraZeneca is comparing the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy and Imfinzi. in mix with other oncology drugs, adding Lynparza and Enhertu.
The company focuses on some of the most challenging cancers. Through constant innovation, AstraZeneca has built one of the most diverse portfolios and projects in the industry, with the potential to catalyze innovation in the practice of medicine and the patient experience.
AstraZeneca’s vision is to redefine cancer care and one day cancer as a cause of death.
References
1. Turner N et al. Capivasertib in hormone receptor-positive breast cancer. NEJM. 2023; 388 : 2058-70.
2. World Health Organization. GLOBOCAN Japan Fact Sheet. Available in: https://gco. iarc. who. int/media/globocan/factsheets/populations/392-japan-fact-sheet. pdf. Retrieved March 2024.
3. National Cancer Institute. Surveillance, Epidemiology, and Final Results Program. Available at: https://seer. cancer. gov/statfacts/html/breast-subtypes. html. Retrieved March 2024.
4. Howell SJ et al. Fulvestrant plus capivasertib compared with placebo after relapse or progression of an aromatase inhibitor in estrogen receptor-positive, HER2-negative metastatic breast cancer (FAKTION). J Clin Oncol. 2022; 23 : 851-64.
5. Hortobagyi GN, et al. Correlative Analysis of Genetic Alterations and Benefits of Everolimus on Human Epidermal Growth Factor Receptor 2 and Hormone Receptor 2 Positive in Advanced Breast Cancer: BOLERO-2 Results. J Clin Oncol. 2016; 34 : 419-26.
6. Millis SZ, et al. Overview of alterations of the phosphatidylinositol-3-kinase pathway in 19,784 assorted artificial tumors. JAMA Oncol. 2016; 2(12):1565-73.
7. Lin M et al. Comparative overall survival of CDK4/6 inhibitors plus endocrine therapy compared with endocrine therapy alone for hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10. 7150/JCA. 48944.
8. World Health Organization. GLOBOCAN Breast Fact Sheet. Available in: https://gco. iarc. who. int/media/globocan/factsheets/cancers/20-breast-fact-sheet. pdf. Retrieved March 2024.
9. Lloyd MR, et al. Mechanisms of resistance to CDK4/6 blockade in complex hormone receptor-positive, HER2-negative breast cancer and opportunities for cure. Clin Cancer Res. 2022; 28(5):821-30.
10. Scabia V, et al. Estrogen receptor-positive breast cancers have patient-specific hormonal sensitivities and depend on progesterone receptors. Nat Commun. 2022; 10. 1038/S41467-022-30898-0.
11. National Comprehensive Cancer Control Network. Clinical Practice Guidelines for Oncology (NCCN Guidelines). Available in: https://www. nccn. org/guidelines/guidelines-detail?category=1
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