AstraZeneca's First-in-Class AKT Inhibitor Capivasertib Receives FDA Approval for HR+/HER2- Advanced Breast Cancer

Nov 17, 2023 09:40 CST Updated 09:40

AstraZeneca

Biopharmaceutical Manufacturer

On November 16, the FDA approved the listing of AstraZeneca's AKT inhibitor Capivasertib.For the treatment of hormone receptorsPositive（HR+）, Human Epidermal Growth Factor Receptor 2Negative（HER2-）Patients with locally advanced or metastatic breast cancer who are receivingEndocrineBasic Treatment PlanProcessDisease Onset or AfterRecurrence or Progression。This also meansAfter more than 40 years of arduous exploration, the AKT target has finally seen a glimmer of hope.

Capivasertib is a potentialfirst-In-classAKT1/2/3 Highly Selective Inhibitor. Activation of the AKT signaling pathway, including alterations in PIK3CA, AKT1, and PTEN, can be observed in many patients with HR+/HER2- advanced breast cancer, but may also occur in patients without these genetic alterations. The AKT signaling pathway is associated with the development of endocrine therapy resistance.

The FDA's approval this time is based onPositive data from a Phase III study codenamed CAPItello-291. TheThe study is a global, multicenter, double-blind, randomized Phase III clinical trial that enrolled a total of 708 patients. It aims to evaluate the efficacy and safety of capivasertib + fulvestrant compared with placebo + fulvestrant in treating HR+/HER2- advanced breast cancer patients whose disease has recurred or progressed during or after AI treatment. The study allows patients to have previously received CDK4/6 inhibitor treatment (at least 51%), but not prior treatment with SERD, mTOR inhibitors, PI3K inhibitors, or AKT inhibitors.

The results showed that, for the primary endpoint, the median PFS in the overall population was 7.2 months in the capivasertib + fulvestrant group and 3.6 months in the placebo + fulvestrant group; capivasertib + fulvestrant reduced the risk of disease progression or death by 40% (HR=0.60 (0.51-0.71, two-sided P＜0.001)).

In terms of ORR, the ORR in the overall population was 22.9% for the capivasertib + fulvestrant group and 12.2% for the placebo + fulvestrant group; in the AKT pathway-altered population, the ORR was 28.8% and 9.7%, respectively. OS data are not yet mature (28% overall maturity).

In terms of safety, in the overall population, the proportions of any adverse events in the capivasertib + fulvestrant group and the placebo + fulvestrant group were 96.6% and 82.3%, respectively; the proportions of any serious adverse events were 16.1% and 8.0%, respectively; the proportions of any adverse events leading to treatment discontinuation were 13.0% and 2.3%, respectively.Common adverse reactions include diarrhea, nausea, rash, fatigue, vomiting, headache, etc.

Recommended Reading

1. AstraZeneca's AKT Inhibitor Capivasertib Submitted for Marketing Approval in China

2. AKT Drug Development Shows Promise: AstraZeneca's Capivasertib Submitted for Market Approval

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