The U.S. Food and Drug Administration (FDA) has approved capivasertib (Truqap) in combination with abiraterone and prednisone for the treatment of adults with PTEN-deficient metastatic androgen pathway modulation-naive or sensitive (mAPMN/S) prostate cancer (previously referred to as metastatic hormone-sensitive prostate cancer [mHSPC]), as detected by an FDA-authorized test. This is the first targeted treatment for patients in this indication.
One in four of these patients have PTEN-deficient tumors, an aggressive form of the disease associated with poor outcomes. PTEN deficiency is an independent risk factor regardless of other clinical characteristics, and can be identified by immunohistochemistry testing at time of diagnosis.
CAPItello-281
The approval was based on the results of the phase III CAPItello-281 trial, which showed a statistically significant 19% reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic progression–free survival of 7.5 months with capivasertib in combination with abiraterone and androgen-deprivation therapy (ADT) vs treatment with abiraterone and ADT with placebo (based on a hazard ratio [HR] of 0.81; 95% confidence interval [CI] = 0.66–0.98; P = .034). Median radiographic progression–free survival was 33.2 months for the capivasertib arm vs 25.7 months for the comparator arm. While overall survival data were immature at the time of the primary analysis, results numerically favored the capivasertib combination vs the comparator arm. The trial will continue as planned to further assess overall survival as a key secondary endpoint.
The safety profile of capivasertib in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each therapy. Grade 3 or higher adverse events occurred in 67% of patients treated with the capivasertib combination, with rash (12.3%) and hyperglycemia (10.3%) being the most frequently reported.
