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Sandy Srinivas, MD


New Angles Explored for Treating High-Volume Metastatic Castration-Sensitive Prostate Cancer

By: Celeste L. Dixon
Posted: Monday, July 10, 2023

The quadruplet regimen of androgen-deprivation therapy (ADT), cabazitaxel/carboplatin, and abiraterone to treat patients with high-volume metastatic castration-sensitive prostate cancer deserves further exploration in randomized phase III studies, based on the early results of the 61-patient phase II CASCARA trial. The study’s primary endpoint was freedom from prostate-specific antigen (PSA)/radiographic disease progression at 1 year, and 77% of patients met that benchmark. The therapy was also well tolerated, according to Charles J. Ryan, MD, of the Prostate Cancer Foundation, California, and colleagues, who presented these findings at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5071).

A total of 61% of the patients had PSA levels of ≤ 0.2 ng/mL at month 7, which surpassed the historic month-7 PSA level ≤ 0.2 ng/mL rate of 45% in the docetaxel arm of the CHAARTED trial, wrote the investigators. That measurement has been a surrogate for survival in other metastatic castration-sensitive prostate cancer studies, they added. In the CASCARA population, the median patient age was 64 years (range, 45–76 years), 21% were Black, the median baseline PSA level was 8.9 ng/mL (range, 0.11–021 ng/mL), and 91% had a Gleason score between 8 and 10.

The homologous recombination repair (HRR) gene mutations that are enriched in metastatic prostate cancer may portend resistance to docetaxel, Dr. Ryan and co-researchers pointed out. In CASCARA, of the 50 patients with evaluable DNA alterations, 18%, 38%, 22%, and 10% had HRR mutations, TP53 mutations, ERG fusions, and SPOP mutations, respectively. And in these subgroups, with the quadruplet therapy, 67%, 77%, 100%, and 100%, respectively, were free from PSA/radiographic disease progression at 1 year.

Disclosure: The study authors’ disclosure information can be found at

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