Docetaxel Improves Survival in Metastatic Hormone-Naïve Prostate Cancer

[Balsam01]

TAKE-HOME MESSAGE

•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

[Hidden]

Thanks for the update. It's easy to focus on median in statistics and ignore the part after that.

This will effect the previous conventional wisdom that doing early Docetaxel should mainly be considered for those that have high tumor burdens. There is a longer-term benefit that is now coming into view. I did early Docetaxel and I'm hoping to be one of those outliers.

[tallguy2 in reply to Hidden]

Me too. Hoping early taxotere chemo has a benefit.

[DarkEnergy]

Yes, but I added Docetaxel after 8 months after ADT + Zytiga, the rationale that it will kill off the "not-so-hormone-sensitive" and/or AR-V7 cancer cells.

[Nicnatno]

I will echo what gregg57 said. I also did chemo upon diagnosis 31 months ago. So far so good. PSA now is 1.1. It was 415 from the start. My Onc is not overly concern. I would def go through it again if I had to.

Nick

[dockam]

Ditto for me, Started ADT in 01/2015 and then first of 15 Taxotere chemos two weeks later. Went from 840.2 to 0.7 in 12/15. Nadir in Summer 2017 @ 0.1 for three months. But, may be castrate resistant - despite restarting ADT in 12/18(took 18 month holiday) PSA went to 7.2 this month. Have Axumin scan on 10/21 to see where PCa is. I'm advocating more chemo than spot Tx or Zytiga

Fight on Brothers

Randy