Upfront Docetaxel - STAMPEDE trial update.

[pjoshea13]

New paper [1] below.

Previously, the CHAARTED study demonstrated that the survival benefit of upfront Docetaxel was confined to those with high volume disease.

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"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."

"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."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/319...

Ann Oncol. 2019 Dec;30(12):1992-2003. doi: 10.1093/annonc/mdz396. Epub 2020 Jan 8.

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 NW1, Ali A2, Ingleby FC3, Hoyle A4, Amos CL5, Attard G6, Brawley CD5, Calvert J5, Chowdhury S7, Cook A5, Cross W8, Dearnaley DP9, Douis H10, Gilbert D5, Gillessen S11, Jones RJ12, Langley RE5, MacNair A5, Malik Z13, Mason MD14, Matheson D15, Millman R5, Parker CC16, Ritchie AWS5, Rush H5, Russell JM17, Brown J18, Beesley S19, Birtle A20, Capaldi L21, Gale J22, Gibbs S23, Lydon A24, Nikapota A25, Omlin A26, O'Sullivan JM27, Parikh O28, Protheroe A29, Rudman S7, Srihari NN30, Simms M31, Tanguay JS32, Tolan S13, Wagstaff J33, Wallace J12, Wylie J34, Zarkar A35, Sydes MR5, Parmar MKB5, James ND36.

Author information

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.

© 2019 THE AUTHORS. Published by Elsevier Ltd on behalf of the European Society for Medical Oncology. This is an open access article under the CC-BY license (creativecommons.org/license....

KEYWORDS:

STAMPEDE trial; docetaxel; hormone naive; metastatic; prostate cancer; randomised control trial

PMID: 31987303 DOI: 10.1093/annonc/mdz396

[6357axbz]

Good post. TY

[timotur]

One key to understanding this study is the definition of low- and high-burden metastasis, which is referenced back to the CHAARTED study.... as I remember defined as:

- low-burden: distant mets in-line with the spine

- high-burden: + distant mets off the spinal centerline (assume meaning mets to ribs, clavicle, etc.)

That's is a pretty broad definition of metastatic burden, and doesn’t differentiate in number of mets (e.g. oligometastatic), or other factors such as LN mets, or Gleason. So prima facia, this only applies to M1, and no inferences can be made about M0 or N1 patients, or based on Gleason score.

[PhilipSZacarias in reply to timotur]

This is quite revelatory. I have always assumed that low burden meant something like less than five 5 mets (oligometastatic) and high burden, greater than that (polymetastatic). Good points. It will be interesting to see what others think. Cheers, Phil

[timotur in reply to PhilipSZacarias]

Well, after going back and looking at e3805, the number of mets was included in the definition of high burden as > 4... but this definition varies by study...

High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Definitions of a high burden of disease have included the presence of visceral metastases, a bone-metastasis burden categorized by site (beyond the axial skeleton) or by a high number of lesions, or a combination of these.9,11,12 In this study, the E3805 study, patients received ADT alone or ADT plus docetaxel at the beginning of ADT for metastatic hormone-sensitive prostate cancer, and stratification was performed prospectively according to high or low burden of metastatic disease.

[Union98]

Thank you for posting. Husband was diagnosed Dec 2016 with four mets. Oncologist gave him the choice of doing 6 rounds or not based on the STAMPEDE/CHARRTED trials even though, at the time, it was not recommended for his low burden. If I remember correctly, high burden was defined as 5 or more mets. I don't remember location of said mets being specified. Husband chose taxotere and it seems to have worked as his PSA was knocked back and with the addition of Zytiga, has remained undetectable since Dec 2017.

[pjoshea13 in reply to Union98]

Excellent! -Patrick

[dockam]

Great news, when I got Dx'd in 2015 (PSA @ 840, GL7 and mets to only L ureter lymph nodes, huge median lobe on prostate) MO said that the results of the studies were coming out and I was Dx'd at right time. Started ADT(Lupron/Casodex) and then 2 weeks later the 1st of 15 Taxotere sessions.

Hit a nadir of 0.1 in Summer of 2017.

Made my 5 yr point with #stageivpca (old stats said 28%)

Despite all those chemos PSA went to 11.7 a few weeks ago and now on Abiraterone. Awaiting latest PSA, blood work show no significant effect so far on blood chemistry.

Fight on Brothers

Randy