Capivasertib plus abiraterone extends rPFS in PTEN-deficient mHSPC

Treatment with capivasertib (Truqap) in combination with abiraterone acetate (Zytiga) and androgen deprivation therapy (ADT) significantly extended radiographic progression-free survival (rPFS) vs placebo with abiraterone plus ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC), according to topline data from the phase 3 CAPItello-281 trial (NCT04493853).¹

Capivasertib is also being studied in the phase 3 CAPItello-280 trial.

AstraZeneca also reported that there was a trend toward an improvement in overall survival (OS), although the data were still immature at the time of data report. The trial remains ongoing to assess this secondary end point.

“Patients with this aggressive form of prostate cancer with tumor PTEN deficiency currently face a particularly poor prognosis, and there is an urgent need for new treatments that improve upon current therapies,” explained principal investigator Karim Fizazi, MD, PhD, Institut Gustave Roussy, and University of Paris Saclay in Villejuif, France, in a news release on the data.¹ “The results seen with capivasertib in combination with abiraterone-prednisone and androgen deprivation therapy in the CAPItello-281 trial represent a step forward for these patients.”

Safety data from the trial has been consistent with the known profiles for each agent. According to AstraZeneca, these data will be presented at an upcoming medical meeting and shared with global regulatory authorities.

“These results show for the first time, that adding an AKT inhibitor to a standard-of-care therapy can provide benefit to patients with a biomarker of PTEN-deficient metastatic hormone-sensitive prostate cancer,” said Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, in the news release.¹ “By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need. It will be important to see greater maturity in key secondary end points including overall survival.”

In total, the double-blind, randomized, placebo-controlled study enrolled 1012 adult patients with mHSPC and PTEN loss.²

To be eligible for enrollment, patients needed to have histologically confirmed de novo mHSPC, PTEN deficiency, an ECOG score of 0 to 1, and ongoing ADT. Patients were excluded if they had prior radical prostatectomy or definitive radiotherapy with therapeutic intent, major surgery within 4 weeks of study start, brain metastases or spinal cord compression, past interstitial lung disease, or any of the pre-specified cardiac criteria.

For the trial, patients were randomly assigned 1:1 to receive 400 mg capivasertib BD on days 1 to 4 of a 28-day treatment cycle or to matching placebo, each in combination with 1000 mg abiraterone daily plus ADT. Treatment is continued until disease progression or unacceptable toxicity.

The primary end point for the study is rPFS, assessed for up to approximately 55 months. Secondary end points include OS, time to the start of first subsequent therapy, symptomatic skeletal event-free survival, and time to pain progression, among other measures.

Final study completion is anticipated for March 2027.

In addition to the CAPItello-281 trial, the phase 3 CAPItello-280 trial is also assessing capivasertib in combination with docetaxel vs placebo plus docetaxel in patients with metastatic castration-resistant prostate cancer. Completion of the study is expected in December 2026.³

References

1. Truqap combination in PTEN-deficient metastatic hormone-sensitive prostate cancer demonstrated statistically significant and clinically meaningful improvement in radiographic progression-free survival in CAPItello-281 phase III trial. News release. AstraZeneca. Published online and accessed November 25, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/truqap-improved-rpfs-in-advanced-prostate-cancer.html

2. Capivasertib+abiraterone as treatment for patients with metastatic hormone-sensitive prostate cancer and PTEN deficiency (CAPItello-281). ClinicalTrials.gov. Last updated July 23, 2024. Accessed November 25, 2024. https://clinicaltrials.gov/study/NCT04493853

3. Study of capivasertib + docetaxel vs placebo + docetaxel as treatment for metastatic castration resistant prostate cancer (mCRPC) (CAPItello280). ClinicalTrials.gov. Last updated October 8, 2024. Accessed November 25, 2024. https://clinicaltrials.gov/study/NCT05348577