Capivasertib Plus Abiraterone/ADT Improves rPFS in PTEN-Deficient mHSPC

Capivasertib Plus Abiraterone/ADT in

PTEN-Deficient mHSPC | Image Credit:

© Sebastian Kaulitzki - stock.adobe.com

Treatment with the combination of capivasertib (Truqap), abiraterone acetate (Zytiga), and androgen deprivation therapy (ADT) led to a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared with placebo plus abiraterone and ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC), meeting the primary end point of the phase 3 CAPItello-281 trial (NCT04493853).¹

Overall survival (OS) data were immature at the time of the analysis, but a trend favoring the capivasertib regimen was observed, according to an announcement from AstraZeneca.

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

Full data from the analysis will be presented at an upcoming medical meeting and shared with global health authorities.

“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,” Karim Fizazi, MD, PhD, of the Institut Gustave Roussy and University of Paris Saclay in Villejuif, France, and principal investigator for the trial, stated in a news 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.”

CAPItello-281 was a double-blind, randomized, placebo-controlled trial that enrolled patients at least 18 years of age with asymptomatic or mildly symptomatic, histologically confirmed de novo hormone-sensitive prostate adenocarcinoma without small-cell tumors diagnosed within 180 days of randomization.² A confirmation of PTEN deficiency via centrally tested immunohistochemistry was required.

Other key inclusion criteria consisted of metastatic disease with evidence of at least 1 bone lesion and/or 1 soft tissue lesion; an ECOG/WHO performance status of 0 or 1; and a life expectancy of at least 12 weeks.

Key exclusion criteria consisted of prior radical prostatectomy or definitive radiotherapy with therapeutic intent for prostate cancer; brain metastases or spinal cord compression, unless spinal cord compression was asymptomatic, treated, stable, and did not require steroids within 4 weeks of enrollment; and a history of interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis.

Investigators enrolled 1012 patients who 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

Along with the primary end point of rPFS, key secondary end points included OS; time to first subsequent therapy or death; symptomatic skeletal event-free survival; time to pain progression; time to castration resistance; time to second progression; quality of life; 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,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, added in a 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 OS.”

In November 2023, the FDA approved capivasertib in combination with fulvestrant (Faslodex) for the treatment of adult patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations, as detected by an FDA-approved test, following progression on at least 1 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://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. 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