Treatment of Metastatic Castration-Resistant Prostate Cancer Without Prior ARPI

This protocol addresses men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed despite castration-level testosterone, have not received an androgen receptor pathway inhibitor (ARPI) for mCRPC, and have no known BRCA1/2 mutation.

Clinical scenario

mCRPC (M1) Castrate testosterone <50 ng/dL Radiological or biochemical progression No prior ARPI for mCRPC No BRCA1/2 mutation

Several systemic agents are approved for mCRPC in this setting. Options span hormone-pathway targeting and cytotoxic approaches, each with prospective evidence of overall survival benefit. Sequencing decisions depend on patient fitness and prior treatment history.

Treatment approach — partial overview

Treatment involves a hormone-pathway–targeting agent or a taxane-based chemotherapy regimen, given alongside ongoing androgen deprivation therapy. The choice between these approaches, and the specific agent, schedule, and sequencing, are specified in the full protocol.

Full regimen details, dosing, and decision algorithm available via the structured protocol below.

Clinical goals

PSA decline ≥50%
Radiographic progression-free survival
No new metastatic lesions

Instant Access to Structured Evidence-Based Regimens

References

Approved agents for the treatment of mCRPC in Europe are docetaxel, abiraterone/prednisolone (AAP), enzalutamide, cabazitaxel, olaparib, niraparib/AAP, talazoparib/enzalutamide, radium-223 and lutetium (177Lu) vipivotide tetraxetan.

The use of chemotherapy with docetaxel and subsequent cabazitaxel in the treatment sequence is recommended and should be applied early enough when the patient is still fit for chemotherapy.

At the final analysis with a median follow-up of 49.2 months, the OS endpoint was significantly positive (34.7 vs. 30.3 months, HR: 0.81, 95% CI: 0.70–0.93, p = 0.0033).

PREVAIL was conducted in a chemo-naive mCRPC population of 1,717 men and showed a significant improvement in both co-primary endpoints, rPFS (HR: 0.186, CI: 0.15–0.23, p < 0.0001), and OS (HR: 0.706, CI: 0.6–0.84, p < 0.001).

The standard first-line chemotherapy is docetaxel 75 mg/m², three-weekly doses combined with prednisone 5 mg twice a day (BID), up to ten cycles.

A ≥50% decrease in PSA was seen in 78% of patients.

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