Background
Phase III, multi-arm multi-stage (MAMS) platform trial (STAMPEDE). 2962 patients randomized; docetaxel arm included 1184 patients with newly diagnosed metastatic (M1, 61%), node-positive (16%), or high-risk M0 (23%) hormone-sensitive prostate cancer starting long-term ADT. Docetaxel arm added after CHAARTED suggested benefit in mHSPC.
Interventions and follow up
Arm A: Docetaxel 75mg/m² IV q3wk × 6 cycles + prednisolone 10mg/day + standard of care ADT
Arm B: Standard of care ADT alone
Primary endpoint: Overall survival (OS)
mFollow up: 43 mo
Arm B: Standard of care ADT alone
Primary endpoint: Overall survival (OS)
mFollow up: 43 mo
Results
OS: HR 0.78, P=.006 (5-yr OS 57% vs 48% in M1 subgroup)
Failure-free survival (FFS): HR 0.61, P<.001
OS (M1 high-volume subgroup): HR 0.73
OS (M0/low-volume subgroup): HR 0.97 — no significant benefit
Failure-free survival (FFS): HR 0.61, P<.001
OS (M1 high-volume subgroup): HR 0.73
OS (M0/low-volume subgroup): HR 0.97 — no significant benefit
Adverse events
Overall grade ≥3 AEs: 52% vs 28% (docetaxel arm)
Hematologic: Febrile neutropenia 15%; one toxic death in docetaxel arm (sepsis)
Neurologic / gastrointestinal: Peripheral neuropathy grade ≥2 17%; diarrhea grade ≥3 5%
Constitutional: Fatigue grade ≥3 5%
Treatment discontinuation: 10% (docetaxel)
Hematologic: Febrile neutropenia 15%; one toxic death in docetaxel arm (sepsis)
Neurologic / gastrointestinal: Peripheral neuropathy grade ≥2 17%; diarrhea grade ≥3 5%
Constitutional: Fatigue grade ≥3 5%
Treatment discontinuation: 10% (docetaxel)
Conclusions
Adding 6 cycles of docetaxel to ADT improved OS in newly diagnosed mHSPC, with the benefit concentrated in high-volume/M1 disease. This was the first European randomized trial to confirm docetaxel intensification in mHSPC, consistent with CHAARTED findings.
Key Limitations
Key Limitations: STAMPEDE enrolled a heterogeneous population including M0 and N+ patients alongside true M1; the OS benefit in M0 or low-volume M1 was not demonstrated. Prednisolone was co-administered with docetaxel (per STAMPEDE protocol), which differs from the docetaxel monotherapy used in CHAARTED and TAX 327 — the steroid contribution is difficult to disentangle. The trial predated ARPI-era intensification; docetaxel + ADT alone is now rarely used as the standard first-line approach in high-volume mHSPC given available triplet data.
Clinical Context
STAMPEDE-doce and CHAARTED established docetaxel + ADT as an early standard for high-volume mHSPC. The benefit is volume-dependent — patients with high-volume metastatic disease (≥4 bone metastases or visceral metastases) derive the greatest benefit. This trial set the foundation for PEACE-1 and ARASENS, which added ARPI to docetaxel + ADT triplet regimens, now preferred for high-volume fit patients. Docetaxel monotherapy + ADT remains an option where ARPI co-pay or access is limiting.
References
References: James ND et al, Lancet 2016