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•This report provides long-term survival data from a randomized trial on androgen deprivation therapy (ADT) plus docetaxel versus ADT alone among patients with low- and high-burden metastatic hormone-sensitive prostate cancer. Compared with the standard-of-care group, the docetaxel group had extended overall (HR, 0.81), failure-free (HR, 0.66), and progression-free (HR, 0.69) survival after a 78.2-month follow-up. There was no evidence of heterogeneity between the two metastatic burden subgroups. At 1 year, grade 3–5 toxicities were similar between the two groups.
•Upfront docetaxel should be considered in the treatment of all metastatic hormone-naïve prostate cancer patients, regardless of metastatic burden.
– Neil Majithia, MD
BACKGROUND
STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
METHODS
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.
RESULTS
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 78.2 months. 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 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).
CONCLUSIONS
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 naïve prostate cancer patients regardless of metastatic burden.
Annals of Oncology
Addition of Docetaxel to Hormonal Therapy in Low- and High-Burden Metastatic Hormone Sensitive Prostate Cancer: Long-Term Survival Results From the STAMPEDE Trial
Ann. Oncol 2019 Sep 27;[EPub Ahead of Print], NW Clarke, A Ali, FC Ingleby, A Hoyle, CL Amos, G Attard, CD Brawley, J Calvert, S Chowdhury, A Cook, W Cross, DP Dearnaley, H Douis, D Gilbert, S Gillessen, RJ Jones, RE Langley, A MacNair, Z Malik, MD Mason, D Matheson, R Millman, CC Parker, AWS Ritchie, H Rush, JM Russell, J Brown, S Beesley, A Birtle, L Capaldi, J Gale, S Gibbs, A Lydon, A Nikapota, A Omlin, JM O'Sullivan, O Parikh, A Protheroe, S Rudman, NN Srihari, M Simms, JS Tanguay, S Tolan, J Wagstaff, J Wallace, J Wylie, A Zarkar, MR Sydes, MKB Parmar, ND James
FDA Approves Darolutamide Plus Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer
