TRUQAP (capivasertib) is approved in combination with fulvestrant for certain HR-positive/HER2-negative breast cancers and AstraZeneca is pursuing regulatory filings in the US and EU to bring it to PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC).

Capivasertib is a 400 mg twice-daily pan-AKT inhibitor given on a 4 days on/3 days off schedule; ongoing Phase III trials include CAPItello-292 for breast cancer and CAPItello-281 for prostate cancer.

CAPItello-281 targets PTEN-deficient de novo mHSPC, representing the first pivotal trial defining this subset, with development continuing alongside CAPItello-292 in breast cancer.

Common adverse reactions are frequent, including diarrhea (about 72%), skin-related reactions (about 58%), and hyperglycemia (about 57%), necessitating monitoring and management plans.

In addition to diarrhea and skin and metabolic effects, a range of laboratory abnormalities led to dose modifications and some treatment discontinuations.

CAPItello-281 showed a statistically significant 19% reduction in the risk of radiographic progression or death, with a median rPFS of 33.2 months versus 25.7 months (HR 0.81, P=0.034).

The primary endpoint demonstrated a 19% risk reduction for radiographic progression or death, with median rPFS extended by about 7.5 months for TRUQAP plus abiraterone and ADT versus control.

Secondary analysis of CAPItello-281 favored the TRUQAP combination, showing improved rPFS and other measures compared with placebo, in the context of first-line therapy for PTEN-deficient mHSPC.

Overall survival data were immature at the primary analysis, but interim results favored TRUQAP, and OS remains a key secondary endpoint as the trial continues.

FDA accepted the supplemental NDA for TRUQAP in this combination in August 2025, based on CAPItello-281 results presented at ESMO and published in a major oncology journal.

ODAC feedback will inform FDA review, and an EU regulatory submission is also under review for TRUQAP in this setting.

Safety and indications note that TRUQAP is currently approved with fulvestrant in breast cancer and carries precautions for hyperglycemia, skin reactions, embryofetal toxicity, and drug interactions with CYP3A modulators/inducers.