FDA Approves First-in-Class Therapy for HR Positive Breast Cancer

The FDA has approved Truqap (capivasertib), along with Faslodex (fulvestrant), to treat patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer. It is indicated for patients with one or more biomarker alterations, including PIK3CA, AKT1 or PTEN.

HR-positive breast cancer is the most common subtype, with more than 65% of tumors considered HR-positive and HER2-low or HER2-negative. The PI3K/AKT/PTEN signaling pathway participates in the regulation of cell growth, and alterations in these biomarkers closely related to tumor progression and resistance to standard therapies. Inhibiting the pathway has the potential to overcome resistance to anti-hormonal therapy and chemotherapy. Collectively, mutations in PIK3CA and AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.

Developed by Astek Pharmaceuticals and partner AstraZeneca, Truqap is an AKT kinase inhibitor. An AstraZeneca spokesperson said Truqap will be available as soon as possible. A price is not available yet, but the spokesperson indicated that the price will reflects the clinical innovation and therapeutic benefit for patients and that patient assistance will be available.

Komal Jhaveri, M.D.

“Patients with advanced HR-positive breast cancer typically experience tumor progression or resistance with widely used first-line endocrine therapies and there is an urgent need to extend the effectiveness of these approaches,” Komal Jhaveri, M.D., medical oncologist and clinical director of early drug development service at Memorial Sloan Kettering Cancer Center, said in a press release. “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.”

The approval was based on results from the phase 3 CAPItello-291, which showed this combination reduced the risk of disease progression or death by 50% compared with Faslodex alone. Results were published earlier this year in The New England Journal of Medicine. Median progression-free survival was 7.3 months for the combination versus 3.1 months for Faslodex alone.

The trial enrolled 708 patients. Confirmed objective response rate (ORR) was 22.9% for the Truqap plus Faslodex arm versus 12.2% for the placebo plus Faslodex arm in the overall trial population, and 28.8% versus 9.7%, respectively, in the biomarker-altered population.

The most frequent adverse events of grade 3 or higher in patients receiving capivasertib–fulvestrant were rash and diarrhea. Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo.

The FDA has also approved FoundationOneCDx to be used as a companion diagnostic for Truqap. The test analyzes more than 300 cancer-related genes for genomic alterations in tumors. The test currently has more than 35 companion diagnostic indications.