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Overall survival with abiraterone acetate plus prednisone vs. docetaxel for the treatment of metastatic hormone-sensitive prostate cancer: An updated network meta-analysis

  • Feyerabend S. 1,
  • Saad F. 2,
  • Ito T. 3,
  • Diels J. 4,
  • Van Sanden S. 4,
  • De Porre P. 5,
  • Roiz J. 6,
  • Abogunrin S. 7,
  • Koufopoulou M. 7,
  • Fizazi K. 8
1 Studienpraxis Urologie, Dept. of Urologic, Oncology, Nürtingen, Germany 2 Centre Hospitalier de l‘Université de Montréal/CRCHUM, Dept. of Urologic, Oncology, Montréal, Canada 3 Janssen, Dept. of Health Economics & Market Access EMEA, High Wycombe, United Kingdom 4 Janssen, Dept. of Health Economics & Market Access EMEA, Beerse, Belgium 5 Janssen, Dept. of Research & Development, Clinical Oncology, Beerse, Belgium 6 Evidera, Dept. of Modelling and Simulation, London, United Kingdom 7 Evidera, Dept. of Meta Research, London, United Kingdom 8 University of Paris Sud, Gustave Roussy, Villejuif, France

Introduction & Objectives

Abiraterone acetate plus prednisone (AA+P) and docetaxel (DOC) are recommended by clinical guidelines as key treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). Given the sparsity of direct comparative evidence in randomized controlled trials (RCTs) of AA+P vs. DOC, we conducted a network meta-analysis (NMA) to compare relative survival benefits of AA+P+androgen deprivation therapy (ADT) and DOC+ADT for mHSPC patients. Results of these analyses have now been updated with newly published results from STAMPEDE.

Materials & Methods

Data from four pivotal RCTs–LATITUDE (AA+P+ADT vs ADT), CHAARTED and GETUG-AFU 15 (DOC+ADT vs. ADT), and STAMPEDE (AA+P+ADT, DOC+ADT and ADT alone) were combined using fixed-effects Bayesian NMA methods to estimate the relative treatment effects on overall survival (OS) of AA+P+ADT vs. DOC+ADT. Several scenario analyses were conducted to account for differences in definitions of populations in the included trials. Results are presented as hazard ratios (HRs) and associated 95% credible intervals (CrIs) and Bayesian probabilities of AA+P+ADT being the better treatment.

Results

The HRs for OS ranged from 0.86 to 0.88, with the Bayesian probability of AA+P+ADT being better than DOC+ADT ranging from 84.8% to 90.6%. Compared with results from our original analyses (HR: 0.91 [95% CrI: 0.76, 1.09]), the HRs of AA+P+ADT vs. DOC+ADT are better when high-risk disease subgroup data from STAMPEDE is used in place of the broader group of metastatic (M1) patients.

Comparison AA+P+ADT vs. ADT DOC+ADT vs. ADT Direct Evidence for AA+P+ADT vs. DOC+P+ADT AA+P+ADT vs. DOC+ADT
 Trial LATITUDE STAMPEDE CHAARTED GETUG-AFU 15 STAMPEDE STAMPEDE    
 Population High-volume & high-risk disease High-risk disease High-risk disease High-volume disease High-volume disease High-volume disease M1 M1 HR [95%-CrI] PAA>DOC
Scenario 1   0.62 (0.51, 0.76) 0.54 (0.41, 0.70)   0.63 (0.49, 0.81) 0.78 (0.54, 1.12) 0.76 (0.62, 0.92) 1.13 (0.77, 1.66)* 0.88 (0.73, 1.07) 90.2%
Scenario 2         0.87 (0.67, 1.13) 84.8%
Scenario 3 0.57 (0.46, 0.71)     0.60 (0.46, 0.78) 0.76 (0.62, 0.92) 1.13 (0.77, 1.66)* 0.88 (0.73, 1.07) 90.6%
Scenario 4         0.86 (0.66, 1.13) 86.1%

Abbreviations: AA= abiraterone acetate; ADT= androgen deprivation therapy; Crl= credible interval; DOC= docetaxel; HR= hazard ratio; P= probability, X= placeholder for STAMPEDE results
*p value= 0.53

Conclusions

Our updated NMA demonstrates that the survival benefits associated with the use of AA+P+ADT versus DOC+ADT remain and are more pronounced in patients with high-risk disease. These findings can provide useful insights to physicians and healthcare payers on the relative survival benefits of newer therapy options for the treatment of men with mHSPC, in particular those with high risk disease.