Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial

​Author(s) Clarke N.W.; Hoyle A.; Ali A.; Ingleby F.C.; Amos C.L. et al.
Source Annals of oncology : official journal of the European Society for Medical Oncology; Sep 2019
DOI 10.1093/annonc/mdz396
BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naive prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.

METHOD(S): We randomly allocated patients in 2:1 ratio to standard-of-care (SOC; control group) or SOC+docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.

RESULT(S): Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n=724) or SOC+docetaxel (n=362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR=0.81, 95% CI 0.69-0.95, P=0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P=0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR=0.66, 95% CI 0.57-0.76, P<0.001) and progression-free survival (HR=0.69, 95% CI 0.59-0.81, P<0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P>0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1year without prior progression).

​CONCLUSION(S): The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naive prostate cancer patients regardless of metastatic burden.Copyright © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

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