Background
Phase III, multi-arm multi-stage (MAMS) platform trial (STAMPEDE). 1917 patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer newly starting long-term ADT: M1 (52%), node-positive M0 (28%), high-risk M0 (20%). Concurrent docetaxel was permitted per local practice. Compares adding abiraterone + prednisolone to standard-of-care ADT.
Interventions and follow up
Arm A: Abiraterone acetate 1000mg/day orally + prednisolone 5mg/day added to standard of care (ADT ± docetaxel)
Arm B: Standard of care (ADT ± docetaxel) alone
Primary endpoint: Overall survival (OS)
mFollow up: 40 mo
Arm B: Standard of care (ADT ± docetaxel) alone
Primary endpoint: Overall survival (OS)
mFollow up: 40 mo
Results
OS: 3-yr OS 83% vs 76%, HR 0.63, P<.001
Failure-free survival (FFS): HR 0.29, P<.001
Metastasis-free survival (M0 subgroup): HR 0.21
Radiographic PFS: HR 0.39
Failure-free survival (FFS): HR 0.29, P<.001
Metastasis-free survival (M0 subgroup): HR 0.21
Radiographic PFS: HR 0.39
Adverse events
Overall grade ≥3 AEs: 47% vs 33%
Cardiovascular / metabolic: Hypertension grade ≥3 14% vs 6%; hypokalemia grade ≥3 6% vs <1%; cardiac events grade ≥3 5% vs 3%; mineralocorticoid excess symptoms requiring management common
Hepatic: Liver toxicity (ALT/AST) 7% vs 1%
Discontinuation due to AEs: 12% vs 7%
Cardiovascular / metabolic: Hypertension grade ≥3 14% vs 6%; hypokalemia grade ≥3 6% vs <1%; cardiac events grade ≥3 5% vs 3%; mineralocorticoid excess symptoms requiring management common
Hepatic: Liver toxicity (ALT/AST) 7% vs 1%
Discontinuation due to AEs: 12% vs 7%
Conclusions
Adding abiraterone + prednisolone to standard ADT significantly improved OS and FFS in newly diagnosed high-risk HSPC across M0 and M1 subgroups, establishing abiraterone intensification as a standard first-line treatment. The trial represented an early and decisive proof of concept for upfront ARPI intensification in hormone-sensitive disease.
Key Limitations
Key Limitations: STAMPEDE enrolled a heterogeneous population (M0 high-risk, N+, and M1) making it broader than the purely metastatic mHSPC populations in other trials. Concurrent docetaxel was permitted in the control arm, making the M1 benefit in a docetaxel-naïve population less cleanly isolable. Abiraterone requires ongoing low-dose prednisolone, introducing steroid-related toxicity and the need for mineralocorticoid monitoring. STAMPEDE's platform design means the comparator arm evolved over time as new standard-of-care arms were added.
Clinical Context
STAMPEDE-abi and LATITUDE (Fizazi K et al, NEJM 2017 in M1 high-risk only) together established abiraterone + ADT as standard first-line mHSPC therapy. STAMPEDE further showed benefit in node-positive and high-risk M0 patients, broadening the indication. The mHSPC landscape has since been further intensified: triplet therapy (PEACE-1: abiraterone + docetaxel + ADT; ARASENS: darolutamide + docetaxel + ADT) is now preferred for high-volume M1 HSPC in fit patients.
References
References: James ND et al, NEJM 2017