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

Research output: Contribution to journalArticle

63 Scopus citations

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. The aggregate data of two phase 3 trials show that patients with a high volume of metastatic castrate naive prostate cancer have poorer overall survival (OS) and benefit from androgen deprivation therapy (ADT) + docetaxel. Low-volume patients have longer OS with ADT alone and no clear benefit with adding docetaxel.

Original languageEnglish (US)
Pages (from-to)847-855
Number of pages9
JournalEuropean urology
Volume73
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

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

ASJC Scopus subject areas

  • Urology

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    Gravis, G., Boher, J. M., Chen, Y. H., Liu, G., Fizazi, K., Carducci, M. A., Oudard, S., Joly, F., Jarrard, D. M., Soulie, M., Eisenberger, M. J., Habibian, M., Dreicer, R., Garcia, J. A., Hussain, M. H. M., Kohli, M., Vogelzang, N. J., Picus, J., DiPaola, R., & Sweeney, C. (2018). 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. European urology, 73(6), 847-855. https://doi.org/10.1016/j.eururo.2018.02.001