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STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer

Giving the hormone-pathway drug abiraterone from the start, alongside standard testosterone suppression, cut deaths by more than a third in men newly diagnosed with high-risk or metastatic prostate cancer.

STAMPEDE is a multi-arm, multi-stage platform trial. This comparison randomised 1,917 men with newly diagnosed locally advanced or metastatic prostate cancer starting androgen deprivation therapy (ADT) to ADT alone or ADT plus abiraterone and prednisolone. Primary endpoint was overall survival.

Overall survival HR was 0.63 (3-year OS 83% vs 76%) and failure-free survival HR 0.29. Alongside LATITUDE, published the same day, it made early intensification of hormone therapy the standard for metastatic hormone-sensitive prostate cancer, and later STAMPEDE analyses extended this to high-risk non-metastatic disease. The platform design itself, testing many questions against one shared control arm, became a model for trial efficiency.

Randomised controlled trialChanged practice1,917 participants
Authors
James ND, de Bono JS, Spears MR, et al.
What it found
  • Overall survival HR 0.63 (95% CI 0.52-0.76); 3-year OS 83% vs 76%.
  • Failure-free survival HR 0.29 (95% CI 0.25-0.34).
  • Benefit consistent in metastatic (M1) and high-risk non-metastatic (M0) subgroups at the primary analysis.
  • Grade 3-5 adverse events 47% vs 33%, driven by hypertension, liver enzyme elevation and cardiovascular events.
  • Later STAMPEDE analysis (Lancet 2022) showed abiraterone for two years in high-risk M0 disease improved 6-year metastasis-free survival from 69% to 82% (HR 0.53).
What it means

Men diagnosed with prostate cancer that has already spread, or that is locally advanced and high risk, should start abiraterone (or another androgen-receptor pathway inhibitor) at the same time as testosterone suppression rather than waiting for resistance. This roughly halves the risk of death over several years. The same platform later showed that docetaxel chemotherapy and, in high-volume metastatic disease, triple therapy also help, and that abiraterone benefits men with high-risk disease treated with radiotherapy.

Be careful
  • Abiraterone requires prednisolone and monitoring for hypertension, hypokalaemia and liver toxicity; cardiovascular risk is higher in older men.
  • Direct comparison with docetaxel (also in STAMPEDE) showed similar OS in metastatic disease, leaving the choice to toxicity and cost.
  • Cost of abiraterone was a barrier until generic versions became available.
  • Optimal duration in non-metastatic disease (two years in STAMPEDE) was chosen empirically.

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