Background
Phase III, open-label, 2×2 factorial RCT. 1173 patients with de novo synchronous metastatic castration-sensitive prostate cancer (mCSPC), all receiving ADT + docetaxel as backbone. Randomized to ± abiraterone + prednisone and ± prostate radiotherapy (RT). High-volume disease in ~75%. This summary focuses on the abiraterone comparison. RT results reported separately (see STAMPEDE-RT).
Interventions and follow up
Arm A: Abiraterone acetate 1000mg/day + prednisone 5mg/day added to ADT + docetaxel (triplet, ± RT)
Arm B: ADT + docetaxel alone (± RT)
Primary endpoint: Radiographic PFS (rPFS) and overall survival (OS), co-primary
mFollow up: 4.4 yr
Arm B: ADT + docetaxel alone (± RT)
Primary endpoint: Radiographic PFS (rPFS) and overall survival (OS), co-primary
mFollow up: 4.4 yr
Results
rPFS (ADT+doce+abi vs ADT+doce): 4.5 vs 2.0 yr, HR 0.54, P<.001
OS (ADT+doce+abi vs ADT+doce): Not reached vs 4.4 yr, HR 0.75, P=.017
rPFS (ARPI-naïve subgroup — no prior abi): HR 0.50
PSA response (<0.2 ng/mL): 75% vs 54%
OS (ADT+doce+abi vs ADT+doce): Not reached vs 4.4 yr, HR 0.75, P=.017
rPFS (ARPI-naïve subgroup — no prior abi): HR 0.50
PSA response (<0.2 ng/mL): 75% vs 54%
Adverse events
Overall grade ≥3 AEs: 63% vs 52% (adding abi)
Cardiovascular / metabolic: Hypertension grade ≥3 21% vs 9%; hypokalemia grade ≥3 7% vs 2%
Hepatic: Liver toxicity 5% vs 2%
Hematologic: Febrile neutropenia (from docetaxel) similar in both arms (~12%)
Treatment discontinuation of abiraterone: 19%
Cardiovascular / metabolic: Hypertension grade ≥3 21% vs 9%; hypokalemia grade ≥3 7% vs 2%
Hepatic: Liver toxicity 5% vs 2%
Hematologic: Febrile neutropenia (from docetaxel) similar in both arms (~12%)
Treatment discontinuation of abiraterone: 19%
Conclusions
Adding abiraterone to docetaxel + ADT (triplet therapy) significantly improved both rPFS and OS in de novo high-volume mCSPC, establishing triplet therapy as the most intensified standard for fit patients with de novo high-volume mHSPC. The absolute OS gain was clinically meaningful in a uniformly high-volume population.
Key Limitations
Key Limitations: The 2×2 factorial design and open-label nature introduce complexity. The backbone includes docetaxel, so the benefit of abiraterone is specifically demonstrated on top of docetaxel + ADT — direct comparison to ARPI + ADT doublets is not available from this trial. High-volume disease was the predominant population (~75%); results in low-volume disease are less robust. The added toxicity of the triplet regimen (63% grade ≥3 AEs) requires careful patient selection and monitoring.
Clinical Context
PEACE-1 and ARASENS (darolutamide + docetaxel + ADT, NEJM 2022) established triplet therapy as the preferred first-line approach for fit patients with high-volume de novo mHSPC. PEACE-1 specifically applies to the abiraterone + docetaxel + ADT combination. Current ESMO guidelines recommend triplet therapy for high-volume M1 mHSPC in patients fit for docetaxel. For low-volume or unfit patients, doublet ARPI + ADT remains standard.
References
References: Fizazi K et al, Lancet 2022