AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has received approval from the European Union (EU) for treating adult patients with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer that harbors one or more PIK3CA, AKT1, or PTEN alterations, following recurrence or progression after an endocrine-based regimen.
This approval from the European Commission follows the positive recommendation by the Committee for Medicinal Products for Human Use, based on results from the CAPItello-291 Phase III trial published in The New England Journal of Medicine.1
In the trial, Truqap combined with Faslodex reduced the risk of disease progression or death by 50% compared to Faslodex with placebo in patients with tumors harboring PI3K, AKT, or PTEN alterations (hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).1
Breast cancer remains the leading cause of cancer death in Europe, with over 140,000 deaths and more than 550,000 new diagnoses in 2022.2 Hormone receptor (HR)-positive breast cancer, which expresses estrogen or progesterone receptors, is the most common subtype, with 70% of tumors being HR-positive and HER2-negative.3 Over 97% of HR-positive breast cancers are ER-positive.4,5 Mutations in PIK3CA, AKT1, and alterations in PTEN frequently occur, affecting about 50% of patients with advanced HR-positive breast cancer.6-8
Dr. Mafalda Oliveira of Vall d’Hebron University Hospital and the Vall d’Hebron Institute of Oncology’s Breast Cancer Group in Barcelona, Spain, stated: “Patients with advanced ER-positive breast cancer often experience progression or resistance with standard endocrine-based treatments. This approval provides new hope for approximately half of ER-positive breast cancer patients in Europe with these biomarkers, and it is crucial for clinicians to test and identify eligible patients who may benefit from this combination.”
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Business Unit, commented: “Truqap is now the first and only AKT inhibitor approved in the European Union for ER-positive breast cancer patients with specific biomarkers. This approval marks a significant advancement in offering a new treatment option for patients in need of innovative therapies.”
The CAPItello-291 trial showed that the safety profile of Truqap plus Faslodex was consistent with previous evaluations of this combination.1
Regulatory reviews for similar indications are ongoing in China and other countries. Truqap in combination with Faslodex is already approved in the US, Japan, and several other countries based on the CAPItello-291 trial.
Financial considerations Following this EU approval, Astex Therapeutics is eligible for a milestone payment from AstraZeneca upon the first commercial sale of the drug in the EU, along with royalties on future sales as per their agreement.
Notes
HR-positive breast cancer HR-positive breast cancer growth is often driven by estrogen receptors, and endocrine therapies targeting ER-driven disease are widely used as first-line treatment, often paired with CDK4/6 inhibitors.9-11 However, resistance to these therapies develops in many patients, limiting treatment options and leading to low survival rates, with approximately 35% of patients living beyond five years post-diagnosis.3,10,12
Research is focused on optimizing endocrine therapy, overcoming resistance, and identifying new treatments for those less likely to benefit from current therapies.
CAPItello-291 CAPItello-291 is a Phase III, double-blind, randomized trial evaluating the efficacy of Truqap with Faslodex versus placebo with Faslodex in locally advanced (inoperable) or metastatic HR-positive (ER-positive and progesterone receptor-positive), HER2-low or negative breast cancer.
The global trial enrolled 708 adults with histologically confirmed HR-positive, HER2-low or negative breast cancer, with recurrence or progression during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial’s primary endpoints were PFS in the overall patient population and in those with PI3K/AKT pathway alterations (PIK3CA, AKT1, or PTEN). Approximately 40% of tumors had these alterations, and 70% of patients had previously received a CDK4/6 inhibitor.
Truqap Truqap is a first-in-class, potent, ATP-competitive inhibitor of all three AKT isoforms (AKT1/2/3), administered at 400mg twice daily on an intermittent schedule of four days on, three days off, based on early trial tolerability and target inhibition results.
Truqap is approved in the US, EU, Japan, and several other countries for treating HR-positive (ER-positive), HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations (PIK3CA, AKT1, or PTEN) following recurrence or progression after an endocrine-based regimen, based on the CAPItello-291 trial. Truqap is also approved in Australia for similar indications.
Truqap is being evaluated in Phase III trials for breast cancer (CAPItello-292) and prostate cancer (CAPItello-280 and CAPItello-281) in combination with established treatments.
Truqap was discovered by AstraZeneca following a collaboration with Astex Therapeutics, the Institute of Cancer Research, and Cancer Research Technology Limited.
Faslodex Faslodex is an endocrine therapy for ER-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse or progression on anti-estrogen therapy.
In the US, EU, and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for HR-positive, HER2-negative advanced or metastatic breast cancer that has progressed after endocrine therapy. Faslodex works by blocking and degrading the estrogen receptor, slowing tumor growth.
Faslodex is approved as monotherapy or in combination with various drugs, including CDK4/6, PI3K, and AKT inhibitors, and is being evaluated in combination with other medicines for HR-positive advanced breast cancer.
AstraZeneca in breast cancer AstraZeneca aims to redefine breast cancer classification and treatment to deliver more effective treatments, with the ambition to eliminate breast cancer as a cause of death.
AstraZeneca’s portfolio includes approved and developing compounds addressing diverse breast cancer biology.
Enhertu (trastuzumab deruxtecan), in collaboration with Daiichi Sankyo, targets HER2-positive and HER2-low metastatic breast cancer, exploring its potential in earlier treatment lines and new settings.
For HR-positive breast cancer, AstraZeneca is advancing treatments with Faslodex and Zoladex (goserelin), and aims to reshape the field with Truqap and the next-generation SERD camizestrant, and is exploring TROP2-directed ADC datopotamab deruxtecan with Daiichi Sankyo.
PARP inhibitor Lynparza (olaparib) is a targeted treatment for early and metastatic breast cancer with BRCA mutations. AstraZeneca and MSD (Merck & Co., Inc. in the US and Canada) are researching Lynparza’s potential in these settings and earlier disease.
To address triple-negative breast cancer, AstraZeneca is evaluating datopotamab deruxtecan alone and with Imfinzi (durvalumab), and Imfinzi with other oncology drugs, including Lynparza and Enhertu.
AstraZeneca in oncology AstraZeneca is revolutionizing oncology with the goal to cure cancer, following science to understand and treat cancer complexities, and delivering life-changing medicines.
Focused on challenging cancers, AstraZeneca’s diverse portfolio and innovative pipeline aim to transform medical practice and patient experience, with a vision to eliminate cancer as a cause of death.
