Capivasertib plus abiraterone in metastatic hormone-sensitive prostate cancer

Results from the CAPItello-281 phase III study, recently published on Annals of Oncology, show that adding capivasertib to abiraterone with androgen deprivation therapy increases radiological progression-free survival in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer.

In this popoluation, PTEN deficiency results in PI3K/AKT pathway activation, providing an independent proliferative drive which cannot be suppressed by androgen receptor pathway inhibitors. CAPItello-281 phase III study investigated the effects if a dual inhibition of PI3K/AKT and androgen receptor pathways in 1519 patients with PTEN-deficient tumors, randomized to receive capivasertib or placebo plus abiraterone and androgen deprivation therapy. Results showed a statistically significant improvement in radiological progression-free survival with capivasertib (median 33.2 months) versus placebo (25.7 months). Post-hoc radiological progression-free survival analyses for loss of PTEN cut-offs of ≥95%, ≥99%, and 100% showed the capivasertib plus abiraterone arm performed consistently across cutoffs, but the placebo plus abiraterone arm performed progressively worse as the cut-off for the degree of PTEN loss was increased. Capivasertib plus abiraterone demonstrated an acceptable safety profile and observed adverse events were consistent with the known toxicity profiles of the individual agents. As authors say, «Results indicated a clear trend in worsening prognosis within the control arm and improved treatment effect derived from the addition of capivasertib to abiraterone with increasing PTEN cut-offs. Consistent additional oncological benefits were observed across secondary endpoints, such as overall survival. These results support combined AKT and androgen receptor inhibition with capivasertib plus abiraterone as a targeted treatment approach in PTEN-deficient metastatic hormone-sensitive prostate cancer».