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 - Archive ouverte HAL Access content directly
Journal Articles European Urology Year : 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

(1) , (2) , (3) , (4) , (5) , (6) , (7) , (8) , (4) , (9) , (6) , (10) , (11) , (12) , (13) , (14) , (15) , (16) , (17) , (18)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Florence Joly
  • Function : Author
  • PersonId : 931500
Jorge Garcia
  • Function : Author

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.

Dates and versions

inserm-02092595 , version 1 (08-04-2019)

Identifiers

Cite

Gwenaëlle Gravis, Jean-Marie Boher, Yu-Hui Chen, Glenn Liu, Karim Fizazi, et al.. 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, 2018, 73 (6), pp.847-855. ⟨10.1016/j.eururo.2018.02.001⟩. ⟨inserm-02092595⟩
101 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More