Capivasertib Improves PFS in PTEN-Deficient mHSPC

Two prostate cancer cells in the final stage of cell division: ©PRB ARTS - stock.adobe.com

Capivasertib (Truqap) given in combination with abiraterone acetate (Zytiga), and androgen deprivation therapy (ADT) showed a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) vs placebo with abiraterone and ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC), according to findings from the phase 3 CAPItello-281 trial (NCT04493853).¹

In addition to the primary end point of the CAPItello-281 trial being met, overall survival (OS) data at the time of analysis were immature. However, there was a trend favoring the capivasertib regimen.

The safety profile of the capivasertib, abiraterone, and ADT regimen was consistent with the known profile of each agent.

“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,” said Karim Fizazi, MD, PhD, of the Institut Gustave Roussy and University of Paris Saclay in Villejuif, France, and principal investigator for the trial, in a press release. “The results seen with capivasertib in combination with abiraterone/prednisone and ADT in the CAPItello-281 trial represent a step forward for these patients.”

Complete results will be presented at a future medical conference and shared with global regulatory agencies.¹

CAPItello-281 Trial

The phase 3, double-blind, randomized, placebo-controlled CAPItello-281 trial sought to evaluate the safety and efficacy of capivasertib, abiraterone, and ADT in male patients aged 18 to 130 years with asymptomatic or mildly symptomatic, histologically confirmed de novo hormone-sensitive prostate adenocarcinoma without small cell tumors diagnosed within 180 days of randomization.²

To enroll in the study, patients were required to have confirmation of PTEN deficiency via centrally tested immunohistochemistry, metastatic disease with evidence of at least 1 bone lesion and/or 1 soft tissue lesion, an ECOG or WHO performance status of 0 or 1, and a life expectancy of at least 12 weeks.

A total of 1012 patients were enrolled in the trial. Patients were randomly assigned to receive capivasertib at 400 mg twice per day on days 1 to 4 of each 28-day cycle plus abiraterone at 1000 mg per day with prednisone/prednisolone and ADT or placebo plus abiraterone with prednisone/prednisolone and ADT.^1,2

The primary end point of the study was rPFS. Secondary end points consisted of OS, symptomatic skeletal event-free survival, quality of life, time to first subsequent therapy or death, time to pain progression, time to castration resistance, time to second progression, and safety.²

“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 mHSPC,” added Susan Galbraith, executive vice president of Oncology research and development at AstraZeneca, in the press 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 OS.”

Capivasertib is currently approved by the FDA for use in combination with fulvestrant for the treatment of adult patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer with at least 1 PIK3CA/AKT1/PTEN-alteration after progression on 1 or more endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.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. November 25, 2024. Accessed November 25, 2024. https://tinyurl.com/y332bne8

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

3. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed November 25, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer