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

Clarke, N. W. et al. (2019) Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Annals of Oncology, 30(123), pp. 1992-2003. (doi: 10.1093/annonc/mdz396) (PMID:31560068) (PMCID:PMC6938598)

Abstract

Abstract 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.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research UK (CRUK_A12459), Medical Research Council (MRC_MC_UU_12023/25), Astellas, Clovis Oncology, Janssen, Novartis,Pfizer and Sanofi-Aventis.
• Keywords: Oncology, hematology.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert
• Authors: Clarke, N. W., Ali, A., Ingleby, F. C., Hoyle, A., Amos, C. L., Attard, G., Brawley, C. D., Calvert, J., Chowdhury, S., Cook, A., Cross, W., Dearnaley, D. P., Douis, H., Gilbert, D., Gillessen, S., Jones, R.J., Langley, R. E., MacNair, A., Malik, Z., Mason, M. D., Matheson, D., Millman, R., Parker, C. C., Ritchie, A. W. S., Rush, H., Russell, J. M., Brown, J., Beesley, S., Birtle, A., Capaldi, L., Gale, J., Gibbs, S., Lydon, A., Nikapota, A., Omlin, A., O'Sullivan, J. M., Parikh, O., Protheroe, A., Rudman, S., Srihari, N. N., Simms, M., Tanguay, J. S., Tolan, S., Wagstaff, J., Wallace, J., Wylie, J., Zarkar, A., Sydes, M. R., Parmar, M. K. B., and James, N. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Annals of Oncology
• Publisher: Oxford University Press (OUP)
• ISSN: 0923-7534
• ISSN (Online): 1569-8041
• Published Online: 08 January 2020
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Annals of Oncology 30(12):1992-2003
• Publisher Policy: Reproduced under a Creative Commons License