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

Advanced Prostate Cancer 

Written by Oliver Sartor MD

This apalutamide trial needs to be viewed in the context of both of the previous abiraterone trials, particularly LATITUDE and STAMPEDE, and also the ENZAMET trial. The ENZAMET trial had a castration-sensitive metastatic population. Enzalutamide had previously been FDA approved for metastatic castrate-resistant docetaxel, metastatic castrate resistance first line, and nonmetastatic castrate resistance. This will represent the fourth FDA approval for enzalutamide in the advanced prostate cancer space.

The most interesting aspect of this trial was not that positive for survival and progression-free survival. There was a hazard ratio of 0.67 representing a reduction in the risk of the death by 33%.

The most interesting aspect of this trial is that a substantial portion of the patients were also treated with docetaxel, and in the analysis of patients who had ADT plus docetaxel plus enzalutamide, there was no additional benefit of the triplet as compared with the doublet of ADT and docetaxel.

This implies some degree of cross-resistance between enzalutamide and docetaxel with regard to prolongation of survival, and that either of these agents may be effective—but not a triplet with ADT, docetaxel, and enzalutamide. At this time, ADT plus enzalutamide represents a new standard of care, but that should also be viewed in context of ADT plus apalutamide, ADT plus abiraterone, and ADT plus docetaxel.

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[CantChoose]

I really struggle to read these. Can someone interpret?

- How many more months does docetaxel typically buy patients?

- I've been told survival curves are virtually identical between enzalutamide vs. docetaxel. Is that still true?

[Schwah]

Do you have the link to the original report? I’m especially interested in the trifecta effect since I did Zytega, chemo and Lupron. I was hoping all three would be better than two out of the three. I know this one involved xtandi and not Zytiga but seems like the results would probably be the same or close.

[Balsam01 in reply to Schwah]

No I do not. There is a citation at the end of the abstract.