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

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.

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]).

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.

The primary end point was OS.

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.

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.

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.

European urology. 2018 Feb 20 [Epub ahead of print]

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, Jorge A Garcia, Maha H M Hussain, Manish Kohli, Nicholas J Vogelzang, Joel Picus, Robert DiPaola, Christopher Sweeney

Centre de Recherche en Cancerologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France. Electronic address: ., Biostatistic, Institut Paoli-Calmettes, Aix-Marseille Universite, Marseille, France., Dana-Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA, USA., University of Wisconsin Carbone Cancer Center, Madison, WI, USA., Gustave Roussy, University of Paris Sud, Villejuif, France., Johns Hopkins University, Baltimore, MD, USA., Department of Medical Oncology, Hopital Europeen Georges Pompidou, Paris, France., Centre Francois Baclesse, Caen, France., Centre Hospitalier Universitaire Rangueil, Toulouse, France., UNICANCER, Paris, France., University of Virginia, Charlottesville, VA, USA., Cleveland Clinic Foundation, Cleveland, OH, USA., University of Michigan Comprehensive Cancer, Ann Arbor, MI, USA., Mayo Clinic, Rochester, MN, USA., Nevada Cancer Research Foundation, Las Vegas, NV, USA., Washington University School of Medicine, St. Louis, MO, USA., University of Kentucky College of Medicine, Lexington, KY, USA., Dana-Farber Cancer Institute, Boston, MA, USA.

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