FDA Approves FoundationOne CDx for Capivasertib Combo in Breast Cancer

The FDA previously approved capivasertib plus fulvestrant in HR-positive, HER2-negative locally advanced or metastatic breast cancer harboring at least 1 PIK3CA, AKT1, or PTEN alteration in November 2023.

The FDA has granted approval to FoundationOne CDx as a companion diagnostic for identifying patients with hormone receptor (HR)–positive, HER2-negative advanced or metastatic breast cancer harboring at least 1 PIK3CA, AKT1, or PTEN alteration who may benefit from treatment with capivasertib (Truqap) plus fulvestrant (Faslodex), according to a press release from Foundation Medicine Inc.¹

In particular, the assay is indicated for use among patients who experienced disease progression following 1 or more lines of endocrine therapy in the metastatic setting. Additionally, FoundationOne CDx can be used for those with disease recurrence on or within a year of finishing adjuvant therapy.

“The prevalence of HR-positive breast cancer means the introduction of new targeted treatment options for this patient population will have an exponential impact,” Shehzin Tietjen, associate director of Corporate Relations at Living Beyond Breast Cancer, said in the press release.¹ “Biomarker testing is such an important component of getting patients on the right therapy for their specific cancer, and we’re encouraged to see additional companion diagnostic indications being approved to help increase patient access to precision medicine.”

Developers designed FoundationOne CDx to screen 324 genes and select rearrangements, thereby helping with identifying potential substitutions, insertion and deletion alterations, and copy number alterations. The press release indicated that the assay is intended exclusively for prescription use, and that it may not guarantee that a patient will be matched to an appropriate therapy. Additionally, a negative reading does not disqualify the potential existence of an alteration.

The FDA previously approved capivasertib plus fulvestrant in HR-positive, HER2-negative locally advanced or metastatic breast cancer harboring at least 1 PIK3CA, AKT1, or PTEN alteration in November 2023.² Supporting data for this approval came from the phase 3 CAPItello-291 trial (NCT04305496), which assessed the regimen among those with disease progression following an aromatase inhibitor-based therapy.

In a population of patients with PIK3CA, AKT1, or PTEN alterations (n = 289), investigators reported a median progression-free survival (PFS) of 7.3 months (95% CI, 5.5-9.0) with capivasertib plus fulvestrant compared with 3.1 months (95% CI, 2.0-3.7) in those treated with placebo plus fulvestrant (HR, 0.50; 95% CI, 0.38-0.65; P = <.0001). Among those whose disease did not harbor an alteration (n = 313), investigators reported that there was also a PFS benefit with the capivasertib-based regimen (HR, 0.79; 95% CI, 0.61-1.02), according to data from an exploratory analysis.

Frequent adverse effects observed in the trial included diarrhea, increased random glucose, decreased lymphocyte counts, decreased hemoglobin, increased fasting glucose, nausea, and fatigue.

“We do need novel drugs in the second-line setting and beyond for HR-positive metastatic breast cancer. The CAPItello-291 phase 3 trial showed that we could potentially have the first agent targeting AKT that is potentially approved and may help to treat certain patients with HR-positive, HER2-negative metastatic breast cancer with activity that is very intriguing, that promises also to have an impact on the quality of life of these patients,” Paolo Tarantino, MD, a medical oncologist from Dana-Farber Cancer Institute, said in an interview with CancerNetwork^®.

In the double-blind, multi-center CAPItello-291 trial, 708 patients were randomly assigned 1:1 to receive 400 mg of capivasertib or matched placebo orally twice a day for 4 days each week as part of a 28-day cycle. Additionally, all patients received 500 mg of fulvestrant intramuscularly on days 1 and 15 of cycle 1 and then every 4 weeks thereafter.

The trial’s primary end point was PFS. Secondary end points included overall survival, overall response rate, duration of response, and safety.

References

1. U.S. FDA approves FoundationOne®CDx as a companion diagnostic for AstraZeneca’s Truqap™ (capivasertib) in combination with Faslodex® (fulvestrant) to identify patients with HR-positive, HER2-negative advanced breast cancer. News release. Foundation Medicine Inc. November 20, 2023. Accessed November 21, 2023. https://shorturl.at/LNSU4
2. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed November 21, 2023. https://shorturl.at/abtH8