ESMO 2017: Docetaxel with androgen suppression for high-risk localized prostate cancer patients who relapsed PSA after radical prostatectomy and/or radiotherapy: A randomized phase III trial
This study was a multicenter, randomized phase III study comparing androgen suppression (triptorelin, every 3 months for 1 year) versus androgen suppression + docetaxel (70 mg/m2 Q3W, 6 cycles). Inclusion criteria included: ≥ 3 rising PSA values >0.2 ng/mL (after radical prostatectomy) or PSA > 1 ng/mL above nadir (after radiotherapy) modified by nadir + 2 ng/ml (RTOG-ASTRO Phoenix) and ≥ 1 of the following criteria: Gleason ≥ 8 disease, PSA doubling time ≤6 months, PSA velocity >0.75 ng/mL/year, positive surgical margins, pN1, time from curative therapy to PSA relapse ≤12 months. Patients were stratified by type of local treatment (radical prostatectomy or radiotherapy) and PSA doubling time (≤ or > 6 months). The primary endpoint was PSA-progression free survival (PSA-PFS) defined as a PSA above 0.2 ng/ml and rise ≥ 50% from baseline confirmed by two subsequent PSA values. Secondary endpoints were PSA response (decrease ≥50%), radiological progression free survival (rPFS), overall survival (OS), and safety.
Between 2003-2007, 250 patients were randomized 1:1 to androgen suppression + docetaxel (n = 125) or androgen suppression alone (n = 125). The median age was 65 years, including 95 patients (38%) undergoing radical prostatectomy, 69 patients (28%) undergoing radiotherapy, and 86 patients (34%) undergoing radical prostatectomy and radiotherapy. Additional risk factors included 29% of men having Gleason ≥8 disease, 54% with PSA doubling time ≤ 6 months, 84% with PSA velocity >0.75 ng/mL/yr, 37% with positive surgical margins, 4% with pN1 disease, and 45% of men with relapse in ≤12 months. More than half of patients had ≥3 risk factors. There was no significant difference in PSA-PFS (HR 0.85, 95%CI 0.62-1.16), PSA response (94% vs 98%), or rPFS (HR 1.01, 95%CI 0.72-1.40) between the two arms; OS outcomes were not mature for analysis. The most common grade ≥3 toxicities among patients receiving androgen suppression + docetaxel was neutropenia (58%), febrile neutropenia (8%) and hair loss (4%).
The authors concluded that despite encouraging results in the metastatic hormone naïve setting, the addition of docetaxel to androgen suppression for patients with biochemical recurrence and high-risk features after primary localized therapy did not result in improved PSA-PFS or rPFS.
Speaker: Stephane Oudard, European Georges Pompidou Hospital, Rene Descartes University, Paris, France
Co-Authors: I. Latorzeff (Toulouse, France) A. Caty (Lille Cedex, France) L. Miglianico (St. Grégoire, France) E. Sevin (Caen, France) A. Hardy Bessard (Plérin sur mer, France) R. Delva (Angers, France) F. Rolland (Saint-Herblain, France) C. Chevreau (Toulouse, France) F. Priou (La Roche sur Yon, France) P. Beuzeboc (Paris, France) G. Gravis (Marseille, France) C. Linassier (Tours, France) P. Gomez (Rouen, France) E. Voog (Le Mans, France) P. Chinet (Rouen, France) X. Muracciole (Marseille, France) C. Abraham Jaillon (Le Chesnay, France)R. Elaidi (Paris, France) S. Culine (Paris, France)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md
at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
References:
1. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.