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Randomized Controlled Trial
. 2019 Dec 1;30(12):1992-2003.
doi: 10.1093/annonc/mdz396.

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

N W Clarke  1 , A Ali  2 , F C Ingleby  3 , A Hoyle  4 , C L Amos  5 , G Attard  6 , C D Brawley  5 , J Calvert  5 , S Chowdhury  7 , A Cook  5 , W Cross  8 , D P Dearnaley  9 , H Douis  10 , D Gilbert  5 , S Gillessen  11 , R J Jones  12 , R E Langley  5 , A MacNair  5 , Z Malik  13 , M D Mason  14 , D Matheson  15 , R Millman  5 , C C Parker  16 , A W S Ritchie  5 , H Rush  5 , J M Russell  17 , J Brown  18 , S Beesley  19 , A Birtle  20 , L Capaldi  21 , J Gale  22 , S Gibbs  23 , A Lydon  24 , A Nikapota  25 , A Omlin  26 , J M O'Sullivan  27 , O Parikh  28 , A Protheroe  29 , S Rudman  7 , N N Srihari  30 , M Simms  31 , J S Tanguay  32 , S Tolan  13 , J Wagstaff  33 , J Wallace  12 , J Wylie  34 , A Zarkar  35 , M R Sydes  5 , M K B Parmar  5 , N D James  36
Affiliations
Randomized Controlled Trial

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

N W Clarke et al. Ann Oncol. .

Erratum in

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.

Keywords: STAMPEDE trial; docetaxel; hormone naive; metastatic; prostate cancer; randomised control trial.

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Figures

Figure 1.
Figure 1.
Consort diagram.
Figure 2.
Figure 2.
Kaplan–Meier curves (solid line) and fitted flexible parametric model estimates (dashed line) for overall survival (left) and failure-free survival (right), by trial arm, for all M1 patients (A,B) low-burden M1 patients (C,D) and high-burden M1 patients (E,F).
Figure 3.
Figure 3.
Effect of docetaxel on overall survival across exploratory sub-groups according to baseline factors.
Figure 4.
Figure 4.
Kaplan–Meier curves (solid line) and fitted flexible parametric model estimates (dashed line), by trial arm, for (A) progression-free survival and (B) metastatic progression-free survival; (C) shows the cumulative incidence function, by trial arm, for prostate cancer death (solid line) and non-prostate cancer death (dashed line).
See this image and copyright information in PMC

References

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