Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel.

[pjoshea13]

New paper (below), but no surprises.

"Patients with a higher burden of metastatic prostate cancer starting androgen deprivation therapy (ADT) have a poorer prognosis and are more likely to benefit from early docetaxel. Low-volume patients have longer overall survival with ADT alone, and the toxicity of docetaxel may outweigh its benefits."

Does "low" end where "high" begins? Or is there a fuzzy middle-volume area, where patients & doctors are going to agonize over whether to use Docetaxel early?

-Patrick

ncbi.nlm.nih.gov/pubmed/294...

Eur Urol. 2018 Feb 20. pii: S0302-2838(18)30102-7. doi: 10.1016/j.eururo.2018.02.001. [Epub ahead of print]

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.

Gravis G1, Boher JM2, Chen YH3, Liu G4, Fizazi K5, Carducci MA6, Oudard S7, Joly F8, Jarrard DM4, Soulie M9, Eisenberger MJ6, Habibian M10, Dreicer R11, Garcia JA12, Hussain MHM13, Kohli M14, Vogelzang NJ15, Picus J16, DiPaola R17, Sweeney C18.

Author information

1

Centre de Recherche en Cancerologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France. Electronic address: [e-mail].

2

Biostatistic, Institut Paoli-Calmettes, Aix-Marseille Universite, Marseille, France.

3

Dana-Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA, USA.

4

University of Wisconsin Carbone Cancer Center, Madison, WI, USA.

5

Gustave Roussy, University of Paris Sud, Villejuif, France.

6

Johns Hopkins University, Baltimore, MD, USA.

7

Department of Medical Oncology, Hopital Europeen Georges Pompidou, Paris, France.

8

Centre Francois Baclesse, Caen, France.

9

Centre Hospitalier Universitaire Rangueil, Toulouse, France.

10

UNICANCER, Paris, France.

11

University of Virginia, Charlottesville, VA, USA.

12

Cleveland Clinic Foundation, Cleveland, OH, USA.

13

University of Michigan Comprehensive Cancer, Ann Arbor, MI, USA.

14

Mayo Clinic, Rochester, MN, USA.

15

Nevada Cancer Research Foundation, Las Vegas, NV, USA.

16

Washington University School of Medicine, St. Louis, MO, USA.

17

University of Kentucky College of Medicine, Lexington, KY, USA.

18

Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

BACKGROUND:

Docetaxel (D) at the time of starting androgen deprivation therapy (ADT) for metastatic castrate naive prostate cancer shows a clear survival benefit for patients with high-volume (HV) disease. It is unclear whether patients with low-volume (LV) disease benefit from early D.

OBJECTIVE:

To define the overall survival (OS) of aggregate data of patient subgroups from the CHAARTED and GETUG-AFU15 studies, defined by metastatic burden (HV and LV) and time of metastasis occurrence (at diagnosis or after prior local treatment [PRLT]).

DESIGN, SETTING, AND PARTICIPANTS:

Data were accessed from two independent phase III trials of ADT alone or ADT+D-GETUG-AFU15 (N=385) and CHAARTED (N=790), with median follow-ups for survivors of 83.2 and 48.2 mo, respectively. The definition of HV and LV disease was harmonized.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary end point was OS.

RESULTS AND LIMITATIONS:

Meta-analysis results of the aggregate data showed significant heterogeneity in ADT+D versus ADT effect sizes between HV and LV subgroups (p=0.017), and failed to detect heterogeneity in ADT+D versus ADT effect sizes between upfront and PRLT subgroups (p=0.4). Adding D in patients with HV disease has a consistent effect in improving median OS (HV-ADT: 34.4 and 35.1 mo, HV-ADT+D: 51.2 and 39.8 mo in CHAARTED and GETUG-AFU15, respectively; pooled average hazard ratio or HR (95% confidence interval [CI]) 0.68 ([95% CI 0.56; 0.82], p<0.001). Patients with LV disease showed much longer OS, without evidence that D improved OS (LV-ADT: not reached [NR] and 83.4; LV-ADT+D: 63.5 and NR in CHAARTED and GETUG-AFU15, respectively; pooled HR (95% CI) 1.03 (95% CI 0.77; 1.38). Aggregate data showed no evidence of heterogeneity of early D in LV and HV subgroups irrespective of whether patients had PRLT or not. Post hoc subgroup analysis was based on aggregated data from two independent phase III randomized trials.

CONCLUSIONS:

There was no apparent survival benefit in the CHAARTED and GETUG-AFU15 studies with D for LV. Across both studies, early D showed consistent effect and improved OS in HV patients.

PATIENT SUMMARY:

Patients with a higher burden of metastatic prostate cancer starting androgen deprivation therapy (ADT) have a poorer prognosis and are more likely to benefit from early docetaxel. Low-volume patients have longer overall survival with ADT alone, and the toxicity of docetaxel may outweigh its benefits.

Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Androgen deprivation therapy; Chemotherapy; Docetaxel; High volume; Low volume; Metastatic castrate naive prostate cancer; Metastatic prostate cancer; Prostate cancer; Volume disease

PMID: 29475737 DOI: 10.1016/j.eururo.2018.02.001

[jkholmes]

Hi . I'm pretty new to my Cancer 5 months in. Gleason 8 with 7 mets is that high volume. Hard to navigate through all this info. My treatment is lupron zytiga with prednisone and Xgeva. So far good results.

[pjoshea13 in reply to jkholmes]

jk,

Depends on the number of mets & their location.

e.g. in the CHAARTED trial, high-volume was:

"... visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis.

-Patrick

[BigRich]

Must be low volume, for John Hopkins could not do the AR-V7 test; for there were not enough circulating cancer cells in my blood.

Rich

[podsart]

Much luck in your upcoming test results Nalakrats!

Excellent point re LV vs HV for those of us who may have micro metastasis and perhaps they are dormant or don’t produce PSA.

The down side in this assessment is SE taxotere potentially greater than benefits for LV. My doc made comment re Zytiga plus prednisone vs taxotere that: rather hit the body 4 to 6 times with chemo than a lifetime on Zytiga plus predinsone.

Previous doc said taxotere can actually change nature of your cancer for better. He believed SE from taxotere would go away.

I am not so sure if these statements are correct, wonder what you guys think

I read on this site that max benefits of taxotere is first 4 treatments, so if can’t complete last 2 still worth it-is this true?

I also read that icing during and taking certain meds and supplements can greatly mitigate SE, don’t know whether this is true for vast majority , most, or some patients.

[BigRich]

I believe, that Zytiga is effective for me, in that; I have been on Zytiga, 3 months, and my PSA has gone from 29.7 to 4.3

Rich