Updated results of GETUG-12, a phase 3 trial of docetaxel-based chemotherapy in high-risk localized prostate cancer, with a 12-year follow-up.

Date 19 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Genitourinary tumours, prostate
Topics Anticancer Agents
Prostate Cancer
Presenter Karim Fizazi
Citation Annals of Oncology (2018) 29 (suppl_8): viii271-viii302. 10.1093/annonc/mdy284
Authors K. Fizazi1, A. Carmel2, F. Joly3, R. Delva4, G. Gravis5, F. Rolland6, F. Priou7, J. Ferrero8, N. Houede9, L. Mourey10, C. Theodore11, I. Krakowski12, J. Berdah13, M. Baciuchka Palmaro14, B. Laguerre15, A. Flechon16, A. Ravaud17, M. Brihoum18, S. Culine19, G. Le Teuff2
  • 1Cancer Medicine, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2Statistics, Gustave Roussy, 94800 - Villejuif/FR
  • 3Na, GINECO & Centre Francois Baclesse Caen, 14000 - Caen/FR
  • 4Medical Oncology Department, Centre Paul Papin, 49100 - Angers/FR
  • 5Medical Oncology, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 6Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - Saint-Herblain/FR
  • 7Medical Oncology, CHD Vendee - Hopital Les Oudairies, 85925 - La Roche sur Yon/FR
  • 8Department Of Medical Oncology, Centre Antoine Lacassagne, 6189 - Nice/FR
  • 9Medical Oncology Departmentical Oncology Department, Institut de cancérologie du Gard, 30029 - Nimes/FR
  • 10Medical Oncology, Institut Universitaire du Cancer -Toulouse- Oncopole, 31059 - Toulouse/FR
  • 11Medical Oncology, Hopital Foch, 92151 - Suresnes/FR
  • 12Medical Oncology & Supportive Care, Institute Bergonié, 33076 - Bordeaux/FR
  • 13Medical Oncology, Oncovar, Hyeres/FR
  • 14Medical Oncology, Hopital Nord, 13915 - Marseille/FR
  • 15Medical Oncology, Centre Eugene - Marquis, 35042 - Rennes/FR
  • 16Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 17Medical Oncology, CHU Bordeaux Hopital St. André, 33000 - Bordeaux/FR
  • 18Clinical research, Unicancer, Kremlin-Bicêtre/FR
  • 19Medical Oncology, Hôpital St. Louis, 75010 - Paris/FR

Abstract

Background

GETUG-12 assessed docetaxel-estramustine in patients with high-risk localized prostate cancer: the primary endpoint of relapse-free survival (RFS) was met (adjusted HR: 0.71 [95% CI: 0.54-0.94], p = 0.017) (Lancet Oncol 2015; 16: 787-94). This analysis updates RFS and assesses clinical events for the first time.

Methods

Eligibility included non-pretreated high-risk localized prostate cancer, defined as ≥ 1 of the following: T3-T4, Gleason ≥8, PSA ≥20 ng/mL, pN + (stratification factors). All 413 patients had a staging pelvic lymph node dissection. Patients were randomized to goserelin for 3 years and 4 cycles of docetaxel 70 mg/m2 + estramustine 10 mg/kg/d days 1-5, every 3 weeks (ADT+DE arm) or goserelin alone (ADT arm). Local therapy (radiotherapy: 87%) was administered at 3 months. Outcomes were tested with a pre-specified order (1: RFS, 2: clinical RFS (cRFS), and 3: metastases-free survival (MFS)) by the fixed-sequence method for controlling the family-wise error rate when conducting tests for multiple endpoints. RFS events: biochemical failures, metastases, proven local relapses, use of salvage treatment, and deaths. cRFS events: metastases, proven local relapses, and deaths. MFS events: metastases and deaths.

Results

With a median follow-up of 12 years [95% CI 11.9–12.2], 233 patients (56%) have had an event. RFS was improved in the ADT+DE arm: 12-year RFS rate: 49.4% [42.5%; 56.3%] in the ADT+DE arm vs 36.3% [29.7%; 43.5%] in the ADT arm (adjusted HR: 0.71 [0.55; 0.93], p = 0.01). The median RFS was 11.6 [9.1; NR] and 8.1 [7.3; 9.6] years. cRFS was also significantly improved in the ADT+DE arm (adjusted HR: 0.75 [0.56 ; 1.00]; p = 0.0491); 12-year rates: 58.8% [51.7% ; 65.6%] vs 50.5% [43.4% ; 57.6%]; median cRFS: 13.9 (13.3-14.9) vs 12.5 (9.9-15.3) years. 12-year MFS rates were 62.2% [55.1%; 68.8%] and 55.8% [48.6%; 62.8%] (adjusted HR: 0.81 [0.60; 1.09]. 12-year PC-specific survival rates were 88.2% [82.5%; 92.2%] and 83.9% [77.4%; 88.8%] (adjusted HR: 0.70 [0.40; 1.22]). The 12-year cumulative rates of second cancers (16.4% vs 18.8%) were similar.

Conclusions

Four cycles of docetaxel-based chemotherapy reduces the risk of clinical relapse or death in men with high-risk localized prostate cancer.

Clinical trial identification

NCT00055731.

Legal entity responsible for the study

UNICANCER.

Funding

UNICANCER.

Editorial Acknowledgement

Disclosure

K. Fizazi: Advisory boards, honorarium: Sanofi. F. Joly: Advisory boards: Sanofi. G. Gravis: Travel expense: Sanofi, Janssen, Astellas. L. Mourey: Travel expense, honoraria: Sanofi. All other authors have declared no conflicts of interest.