FDA approves Truqap with fulvestrant for breast cancer subset
The FDA approved capivasertib as part of combination therapy for certain patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer.
The indication applies to use of capivasertib (Truqap, AstraZeneca) with fulvestrant for adults who have one or more PIK3CA/AKT1/PTEN alterations as detected by an FDA-approved test, and whose disease progressed on at least one endocrine-based regimen in the metastatic setting or recurred on or within 12 months of adjuvant therapy completion.
The FDA also approved the FoundationOne CDx assay (Foundation Medicine) as a companion diagnostic device to identify patients who may benefit from treatment with this combination.
The agency based approval on results of the randomized CAPItello-291 trial, which included 708 patients with locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. About 40% (n = 289) of study participants had tumors with PIK3CA/AKT1/PTEN alterations.
All study participants experienced disease progression on aromatase inhibitor-based treatment. Patients could have received up to two lines of endocrine therapy and one line of chemotherapy for locally advanced or metastatic disease.
Researchers randomly assigned study participants to capivasertib 400 mg or placebo orally twice daily for 4 days, followed by 3 days off, each week for 28-day cycles. All patients received fulvestrant 500 mg administered intramuscularly on days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.
Investigator-assessed PFS in the overall cohort, and in the subgroup of patients whose tumors had PIK3CA/AKT1/PTEN alterations, served as key efficacy outcomes.
Among those with PIK3CA/AKT1/PTEN-altered tumors, results showed median PFS of 7.3 months with capivasertib-fulvestrant and 3.1 months with placebo-fulvestrant (HR = 0.5; 95% CI, 0.38-0.65).
An exploratory analysis of patients whose tumors did not have PIK3CA/AKT1/PTEN alterations showed no significant difference in PFS with capivasertib or placebo (HR = 0.79; 95% CI, 0.61-1.02), suggesting a PFS benefit observed in the overall cohort was driven by the subgroup of patients with PIK3CA/AKT1/PTEN alterations.
Adverse reactions reported among at least 20% of patients included diarrhea, cutaneous adverse reactions, increased random glucose, decreased lymphocytes, decreased hemoglobin, increased fasting glucose, nausea, fatigue, decreased leukocytes, increased triglycerides, decreased neutrophils, increased creatinine, vomiting and stomatitis.
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