Abstract
BackgroundSTAMPEDE 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.MethodsWe 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.ResultsBetween 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).ConclusionsThe 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.
Highlights
The primary analysis of STAMPEDE’s ‘docetaxel comparison’, reporting an improvement in survival, was triggered by reaching a pre-specified number of control group deaths [1]
The Intermediate Clinical Endpoints in Cancer of the Prostate surrogacy work showed that measures based on metastatic progression could be used as a surrogate for survival in patients presenting with M0 disease, allowing trials in that setting to achieve increased power sooner [2]
Since that initial STAMPEDE report, first-line systemic combination treatment options given with androgen deprivation therapy (ADT) in metastatic hormone naıve prostate cancer have expanded to include abiraterone, enzalutamide and apalutamide as well as docetaxel [1, 3,4,5,6,7,8]
Summary
The primary analysis of STAMPEDE’s ‘docetaxel comparison’, reporting an improvement in survival, was triggered by reaching a pre-specified number of control group deaths [1]. Metastatic burden sub-group analyses of the CHAARTED and GETUG-15 trials have led some to conclude that docetaxel should not be given as a first-line treatment of patients presenting with ‘low metastatic burden’ disease [3, 9,10,11]. This represents $40% of patients presenting with de novo mHNPC [12, 13]. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional
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