CAPItello-281 Trial Design and Efficacy Data in mHSPC

The phase 3 CAPItello-281 trial (NCT04493853) met its primary end point by showing that the addition of capivasertib (Truqap) to abiraterone (Zytiga) and prednisone significantly improved radiographic progression-free survival (rPFS) vs abiraterone and prednisone alone in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC). In this video, Scott Sellinger, MD, FACS, highlights the efficacy results from the pivotal phase 3 trial.

The study enrolled more than 1000 patients with de novo metastatic hormone-sensitive disease, a population that often presents with more aggressive and difficult-to-treat cancer. Patients were required to have significant PTEN loss, defined in the trial as at least 90% loss of PTEN staining, and many had high-risk disease features, including visceral metastases. Patients were randomly assigned to receive either standard therapy with abiraterone, prednisone, and androgen deprivation therapy (ADT) or treatment intensification with the addition of capivasertib. He emphasizes that the control arm represented a strong active comparator rather than a placebo, as abiraterone plus ADT is already an effective standard treatment option in mHSPC. T

Discussing the clinical significance of the findings, Sellinger highlights the improvement in rPFS observed with the addition of capivasertib, noting that the median rPFS was 33.2 months in the treatment arm vs 25.7 months in the control arm (HR, 0.81; 95% CI, 0.66 to 0.98; P = .034). He explains that delaying radiographic progression is particularly meaningful because it can extend the period patients remain in the hormone-sensitive setting and potentially delay the transition to castration-resistant disease. While overall survival remains an important outcome, Sellinger notes that rPFS also provides insight into maintaining quality of life by postponing disease progression. He adds that improvements in related end points, such as time to PSA progression and symptomatic skeletal event-free survival, are consistent with the overall rPFS benefit demonstrated in the trial.