Docetaxel for hormone-naïve prostate cancer (PCa): Results from long-term follow-up of non-metastatic (M0) patients in the STAMPEDE randomised trial

Abstract

Background: STAMPEDE previously reported that adding upfront docetaxel (Doc) improved overall survival (OS) for locally advanced and metastatic patients (pts) starting long‐term androgen deprivation therapy (ADT). We report the long‐term outcomes for M0 pts using metastatic progression‐free survival (mPFS) as primary outcome, previously shown to be a surrogate for OS in M0 pts. Methods: Standard‐of‐care (SOC) was ADT +/‐ radical radiotherapy (RT) to the prostate. 460 SOC and 230 SOC+Doc pts were recruited with 2:1 randomised stratified allocation. Standard survival intention‐to‐treatment analysis methods used Cox regression models adjusted for all stratification factors, with emphasis on restricted mean survival time (RMST) for non‐proportional (non‐PH) hazards. There was 70% power (2‐sided a=0.05) to detect HR=0.70 for mPFS (=new metastases, skeletal related events or PCa death). Secondary outcome measures included failure free survival (FFS) and progression free survival (PFS = mPFS or locoregional progression). Results: Median follow‐up was∼6.5yr compared to ∼3.5yr when last reported, with 142 mPFS events (a 54% increase) on SOC. There was no good evidence of an advantage of SOC+Doc over SOC on mPFS (HR=0.89, 95% CI 0.66‐1.19, P=0.425); with 5yr mPFS 82% in SOC+Doc vs. 77% SOC. Secondary outcomes showed evidence that SOC+Doc improved FFS (HR=0.70, 95% CI 0.55‐0.88, P=0.002) and PFS (non‐PH P=0.033, RMST difference=5.8 months, 95% CI 0.5‐11.2, P=0.031). There was no good evidence of a benefit of SOC+Doc on OS (125 SOC deaths;HR=0.88, 95% CI 0.64‐1.21, P=0.442). There was no evidence that SOC+Doc increased late toxicity compared to SOC: after 1yr, G3‐5 toxicity reported for 29% SOC and 30% SOC+Doc. The impact of SOC RT (nominated prior to randomisation) with and without SOC+Doc will also be detailed by subgroup. Conclusions: There is robust evidence SOC+Doc improves FFS and PFS (which we have previously shown increases Quality Adjusted Life Years). There is however no good evidence that this translates into benefit for longer‐term outcomes (OS or mPFS). The benefits of upfront SOC+Doc for improved FFS and PFS with no excess late toxicity may contribute to treatment discussions.