By Tyler Patchen

Pictured: AstraZeneca office in Gothenburg, Sweden
AstraZeneca announced Friday that its adenosine triphosphate (ATP)-competitive inhibitor Truqap (capivasertib), in combination with its endocrine therapy Faslodex (fulvestrant), has been approved by the FDA to treat adults with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer.
According to AstraZeneca, the first-in-class inhibitor of all three AKT isoforms (AKT1/2/3) “has potential to reshape treatment for breast cancer patients” with specific biomarker alterations (PIK3CA, AKT1 or PTEN). The company also announced that the FDA has approved a “companion” diagnostic test meant to detect the “relevant” alterations.
The FDA approval was based on the CAPItello-291 Phase III trial, which showed that the combination of Faslodex and Truqap reduced the risk of disease progression or death by 50%, compared to Faslodex alone, in patients with tumors having PI3K/AKT pathway biomarker alterations.
“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,” Komal Jhaveri, a medical oncologist at Memorial Sloan Kettering Cancer Center, said in a statement.
The results of the CAPItello-291 trial were published in The New England Journal of Medicine, which showed the median progression-free survival was recorded at 7.3 months in the combination group, while 3.1 months were reported in the Faslodex-only group, earning a p-value of p<0.001. Adverse events included rash and diarrhea, with 13% of patients having events that led to a discontinuation in the combination group.
“The rapid U.S. approval of Truqap reinforces the important role of the PI3K/AKT 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,” Dave Fredrickson, the executive vice president of AstraZeneca’s oncology business unit, said in a statement. “As a first-in-class medicine, this approval provides a critical new option for patients in the U.S. 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.”
The combination was granted FDA priority review in June 2023 and is also being reviewed by several other regulatory agencies, including Brazil, Canada, Israel, Australia, the U.K., Singapore and Switzerland. Regulators in the European Union, China and Japan are also reviewing regulatory applications for the drug combo.
AstraZeneca also noted in its announcement that Astex Therapeutics will be able to get a milestone payment on the first commercial sale of the drug in the U.S. and royalties on future sales.
Last week, AstraZeneca’s Imfinzi and Genentech’s Avastin showed positive survival results in hepatocellular carcinoma. However, earlier this week a combination of Imfinzi and chemoradiotherapy did not reach its primary endpoint for treating non-small cell lung cancer.