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, A Ali, F C Ingleby, A Hoyle, C L Amos, G Attard, C D Brawley, J Calvert, S Chowdhury, A Cook, W Cross, D P Dearnaley, H Douis, D Gilbert, S Gillessen, R J Jones, R E Langley, A MacNair, Z Malik, M D Mason, D Matheson, R Millman, C C Parker, A W S Ritchie, H Rush, J M Russell, J Brown, S Beesley, A Birtle, L Capaldi, J Gale, S Gibbs, A Lydon, A Nikapota, A Omlin, J M O'Sullivan, O Parikh, A Protheroe, S Rudman, N N Srihari, M Simms, J S Tanguay, S Tolan, J Wagstaff, J Wallace, J Wylie, A Zarkar, M R Sydes, M K B Parmar, N D James, N W Clarke, A Ali, F C Ingleby, A Hoyle, C L Amos, G Attard, C D Brawley, J Calvert, S Chowdhury, A Cook, W Cross, D P Dearnaley, H Douis, D Gilbert, S Gillessen, R J Jones, R E Langley, A MacNair, Z Malik, M D Mason, D Matheson, R Millman, C C Parker, A W S Ritchie, H Rush, J M Russell, J Brown, S Beesley, A Birtle, L Capaldi, J Gale, S Gibbs, A Lydon, A Nikapota, A Omlin, J M O'Sullivan, O Parikh, A Protheroe, S Rudman, N N Srihari, M Simms, J S Tanguay, S Tolan, J Wagstaff, J Wallace, J Wylie, A Zarkar, M R Sydes, M K B Parmar, N D James

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.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

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).

References

    1. James ND, Sydes MR, Clarke NW. et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016; 387(10024): 1163–1177.
    1. Xie W, Regan MM, Buyse M. et al. Metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer. J Clin Oncol 2017; 35(27): 3097–3104.
    1. Sweeney CJ, Chen YH, Carducci M. et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; 373(8): 737–746.
    1. Fizazi K, Tran N, Fein L. et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 2019; 20(5): 686–700.
    1. Chi KN, Agarwal N, Bjartell A. et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 2019; 381(1): 13–24.
    1. Davis ID, Martin AJ, Stockler MR. et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 2019; 381(2): 121–131.
    1. James ND, de Bono JS, Spears MR. et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 2017; 377(4): 338–351.
    1. Vale CL, Burdett S, Rydzewska LHM. et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol 2016; 17(2): 243–256.
    1. Kyriakopoulos CE, Chen YH, Carducci MA. et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 2018; 36(11): 1080–1087.
    1. Gravis G, Boher JM, Chen YH. et al. Burden of metastatic castrate naive prostate cancer patients, to identify men more likely to benefit from early docetaxel: further analyses of CHAARTED and GETUG-AFU15 studies. Eur Urol 2018; 73(6): 847–855.
    1. National Comprehensive Cancer. Network Clinical Practice Guidelines in Oncology-Prostate cancer Version 4.2019. 2019; (15 September 2019, date last accessed).
    1. Hoyle AP, Ali A, James ND. et al. Abiraterone in “high-” and “low-risk” metastatic hormone-sensitive prostate cancer. Eur Urol 2019. doi: 10.1016/j.eururo.2019.08.006.
    1. Parker CC, James ND, Brawley CD. et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet 2018; 392(10162): 2353–2366.
    1. Prostate cancer: diagnosis and management [NG131]: NICE 2019; (15 September 2019, date last accessed).
    1. Parker C, Gillessen S, Heidenreich A, ESMO Guidelines Committee et al.Cancer of the prostate: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26(Suppl 5): v69.
    1. European Association of Urology Guidelines: Prostate Cancer 2019; (15 September 2019, date last accessed).
    1. Fine JP, Gray RJ.. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94(446): 496–509.
    1. Royston P, Parmar MK.. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med 2011; 30(19): 2409–2421.
    1. Gravis G, Boher JM, Joly F. et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non-castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol 2016; 70(2): 256–262.
    1. Finianos A, Gupta K, Clark B. et al. Characterization of differences between prostate cancer patients presenting with de novo versus primary progressive metastatic disease. Clin Genitourin Cancer 2017. doi: 10.1016/j.clgc.2017.08.006.
    1. Ali A, Hoyle A, Mistry H, Clarke NW.. Importance of non-regional lymph nodes in assigning risk in primary metastatic prostate cancer. BJU Int 2019; 123(1): 65–73.
    1. Sydes MR, Spears MR, Mason MD. et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol 2018; 29(5): 1235–1248.

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