In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC.
Patients and Methods
Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life.
Results
Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75.
Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life.
Results
Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75.
Conclusion
C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.
Oudard S1, Fizazi K2, Sengeløv L3, Daugaard G4, Saad F5, Hansen S6, Hjälm-Eriksson M7, Jassem J8, Thiery-Vuillemin A9, Caffo O10, Castellano D11, Mainwaring PN12, Bernard J13, Shen L14, Chadjaa M15, Sartor O16.
Author Information
1Stéphane Oudard, Georges Pompidou European Hospital, Rene Descartes University
2Karim Fizazi, Institut Gustave Roussy, University of Paris Sud, Villejuif
3Lisa Sengeløv, Herlev Hospital, Herlev
4Gedske Daugaard, Copenhagen University Hospital, Rigshospitalet, Copenhagen
5Fred Saad, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
6Steinbjørn Hansen, Odense University Hospital, Odense, Denmark
7Marie Hjälm-Eriksson, Karolinska University Hospital, Stockholm, Sweden
8Jacek Jassem, Medical University of Gdansk, Gdansk, Poland
9Antoine Thiery-Vuillemin, Centre Hospitalier Universitaire Minjoz Besançon, Besançon, France
10Orazio Caffo, Santa Chiara Hospital, Trento, Italy
11Daniel Castellano, University Hospital de Octubre, Madrid, Spain
12Paul N. Mainwaring, Icon Cancer Care, Brisbane, Queensland, Australia
13John Bernard, Sanofi, Cambridge, MA
14Liji Shen, Sanofi, Bridgewater, NJ
15Mustapha Chadjaa; Sanofi, Paris
16Oliver Sartor, Tulane Cancer Center, New Orleans, LA.
C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.
Oudard S1, Fizazi K2, Sengeløv L3, Daugaard G4, Saad F5, Hansen S6, Hjälm-Eriksson M7, Jassem J8, Thiery-Vuillemin A9, Caffo O10, Castellano D11, Mainwaring PN12, Bernard J13, Shen L14, Chadjaa M15, Sartor O16.
Author Information
1Stéphane Oudard, Georges Pompidou European Hospital, Rene Descartes University
2Karim Fizazi, Institut Gustave Roussy, University of Paris Sud, Villejuif
3Lisa Sengeløv, Herlev Hospital, Herlev
4Gedske Daugaard, Copenhagen University Hospital, Rigshospitalet, Copenhagen
5Fred Saad, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
6Steinbjørn Hansen, Odense University Hospital, Odense, Denmark
7Marie Hjälm-Eriksson, Karolinska University Hospital, Stockholm, Sweden
8Jacek Jassem, Medical University of Gdansk, Gdansk, Poland
9Antoine Thiery-Vuillemin, Centre Hospitalier Universitaire Minjoz Besançon, Besançon, France
10Orazio Caffo, Santa Chiara Hospital, Trento, Italy
11Daniel Castellano, University Hospital de Octubre, Madrid, Spain
12Paul N. Mainwaring, Icon Cancer Care, Brisbane, Queensland, Australia
13John Bernard, Sanofi, Cambridge, MA
14Liji Shen, Sanofi, Bridgewater, NJ
15Mustapha Chadjaa; Sanofi, Paris
16Oliver Sartor, Tulane Cancer Center, New Orleans, LA.