FDA Approves Prostate Cancer Combo That Warranted Advisory Meeting

The FDA approved capivasertib (Truqap) in combination with abiraterone (Zytiga) and prednisone for PTEN-deficient prostate cancer, the agency announced on Friday.

Approval stipulates use in metastatic hormone-sensitive prostate cancer — or what is now pithily being called metastatic androgen pathway modulation-naive or -sensitive prostate cancer.

In the phase III CAPItello-281 trial, adding capivasertib to abiraterone in this patient population improved radiographic progression-free survival (PFS) from 25.7 months to 33.2 months (HR 0.81, 95% CI 0.66-0.98, P=0.034). Overall survival (OS) results were immature, though an interim analysis showed no significant OS benefit (HR 0.90, 95% CI 0.71-1.15).

That 7-month PFS improvement without an OS benefit raised enough questions for FDA reviewers to warrant an advisory committee meeting.

In the absence of a large PFS improvement, “a statistically significant improvement in OS may be needed to support a clinically meaningful treatment effect,” agency reviewers wrote in briefing documents ahead of the April meeting.

But members of the Oncologic Drugs Advisory Committee (ODAC) overwhelmingly endorsed the combination.

“My impression is that the 7-plus months is meaningful,” panelist William Gradishar, MD, of Northwestern Feinberg School of Medicine in Chicago, said at the time.

The endorsement from ODAC — with a 7-1 vote no less — all but assured the FDA would approve the combination for PTEN-deficient tumors, which occur in about 25% of this subset of prostate cancer patients.

“Patients with PTEN-deficient metastatic hormone-sensitive prostate cancer, now called metastatic androgen pathway modulation-naive or -sensitive prostate cancer, experience faster progression and worse prognosis than those without PTEN deficiency,” CAPItello-281 investigator Daniel George, MD, of Duke Cancer Institute in Durham, North Carolina, said in a press release from drugmaker AstraZeneca.

“Keeping patients with this form of prostate cancer in remission and free from disease progression as long as possible is a high priority,” added George. “Today’s landmark approval of the capivasertib combination as the first and only targeted treatment option for these patients represents a significant clinical advance with the potential to improve their lives and change the course of disease.”

Capivasertib was first approved in 2023 for locally advanced or metastatic breast cancer in patients whose tumors harbor PIK3CA, AKT1, or PTEN alterations, while abiraterone initially gained approval for prostate cancer back in 2011.

In CAPItello-281, grade ≥3 adverse events (AEs) occurred in 67% of patients treated with capivasertib plus abiraterone — rash (12.3%) and hyperglycemia (10.3%) were most common. The FDA said that the prescribing information also includes warnings and precautions related to hyperglycemia, diarrhea, cutaneous AEs, and embryo-fetal toxicity.

A companion diagnostic device — the VENTANA PTEN (SP218) RxDx Assay — was also approved to identify patients with PTEN-deficient tumors.

Staff writer Mike Bassett contributed to this report.

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