Daniel George, MD, on the significance of the capivasertib approval for PTEN-deficient prostate cancer

In this video, Daniel J. George, MD, discusses findings from the phase 3 CAPItello-281 trial (NCT04493853) that supported the recent FDA approval of capivasertib (Truqap) in combination with abiraterone acetate (Zytiga) and prednisone in PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer.¹

George explained that PTEN loss is present in approximately 25% of patients with advanced prostate cancer, making it a clinically important biomarker. In the CAPItello-281 trial, investigators screened roughly 6,200 patients with de novo metastatic androgen pathway modulation-naïve disease and identified approximately 1,500 with PTEN-deficient tumors, defined by at least 90% loss of PTEN protein on biopsy. Nearly 1,000 patients were randomly assigned to receive standard-of-care abiraterone, prednisone, and androgen deprivation therapy (ADT) with either capivasertib or placebo, with radiographic progression-free survival (rPFS) serving as the primary end point.

According to George, the trial met its primary end point, demonstrating a 7.5-month improvement in median rPFS with the addition of capivasertib (median 33.2 vs 25.7 months; HR, 0.81; 95% CI, 0.66 to 0.98; P = .034). He emphasized that the 25.7-month median rPFS observed in the control arm was substantially shorter than the approximately 36 months or longer reported in many previous studies of metastatic hormone-sensitive prostate cancer, providing prospective evidence that PTEN-deficient disease represents a particularly aggressive subtype. He noted that patients in the control arm also experienced earlier development of castration-resistant disease (HR, 0.77; 95% CI, 0.63 to 0.94), symptomatic skeletal events (HR, 0.82; 95% CI, 0.66 to 1.02), and the need for subsequent therapy (HR, 0.91; 95% CI, 0.75 to 1.11).

George said these findings underscore the importance of identifying PTEN-deficient disease at diagnosis, as standard therapy alone appears insufficient for this high-risk population. Although he acknowledged that larger treatment effects are always desirable and that longer follow-up may identify subgroups with even greater benefit, he stressed that delaying disease progression by 7.5 months represents meaningful progress for patients with this aggressive form of prostate cancer. He added that this clinical benefit was a key consideration during the FDA's Oncologic Drugs Advisory Committee discussion and reinforces the value of capivasertib for this patient population.

REFERENCE

1. FDA approves capivasertib with abiraterone and prednisone for PTEN-deficient androgen pathway modulation-naïve or -sensitive prostate cancer. News release. US Food & Drug Administration. June 12, 2026. Accessed July 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-abiraterone-and-prednisone-pten-deficient-androgen-pathway-modulation