Home
Resources
Publications
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

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

Gwenaelle Gravis, Jean-Marie Boher, Yu-Hui Chen, Glenn Liu, Karim Fizazi, Michael A Carducci, Stephane Oudard, Florence Joly, David M Jarrard, Michel Soulie, Mario J Eisenberger, Muriel Habibian, Robert Dreicer, etc.

Eur Urol. 2018 Jun;73(6):847-855.

PMID: 29475737

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP144413581	ADT		144413-58-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: