Darolutamide and enzalutamide are second-generation androgen receptor inhibitors with activity in men with castrate-resistant prostate cancer (CRPC) and different toxicity profiles.
ODENZA is a prospective, randomized, multicenter, cross-over, phase 2 trial designed to assess preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic CRPC (mCRPC).
Patients were randomized 1:1 to receive either darolutamide 1200 mg/d for 12 wk followed by enzalutamide 160 mg/d for 12 wk or enzalutamide followed by darolutamide. In both arms, the second treatment was given in absence of cancer progression.
The primary endpoint was patient preference between the two drugs, as assessed by a preference questionnaire (p value calculated with the Prescott test). After week 24, patients entered an extension period during which they received their preferred treatment until progression or toxicity. The main secondary objectives included reasons for patient preference, response at week 12, tolerance of each drug, and measurement compared with baseline of cognitive outcomes assessed using tablet questionnaires.
Overall, 249 patients, with a median age of 72 yr, were randomized. Among the 200 patients who fulfilled the preplanned criteria for the evaluation of the primary endpoint of preference, 97 (49% [41; 56]), 80 (40% [33; 47]), and 23 (12% [7; 16]) chose darolutamide, chose enzalutamide, and had no preference, respectively (p = 0.92). Reduced fatigue, easier administration, and better quality of life were the main criteria that influenced patient choice. A moderate benefit in episodic memory from darolutamide was observed for the acquisition of new information (least square [LS] means difference = 2.2, effect size = 0.5) and for the recall of that information after a brief delay (LS means difference = 0.7, effect size = 0.3). Using the Brief Fatigue Inventory questionnaire, patients reported greater fatigue with enzalutamide (3.3 [3.0; 3.6]) than with darolutamide (2.7 [2.4; 3.0]). There was no difference in terms of depression, seizures, and falls.
The study did not show a difference in preference between the two treatments. In men with mCRPC, darolutamide was associated with a clinically meaningful benefit in episodic memory and less fatigue compared with enzalutamide.
Preference between darolutamide and enzalutamide was well balanced in men with castrate-resistant prostate cancer. Darolutamide was associated with a significant benefit in verbal learning and less fatigue compared with enzalutamide.
European urology. 2023 Jun 02 [Epub ahead of print]
Emeline Colomba, Sarah Flora Jonas, Jean-Christophe Eymard, Rémi Delva, Pierre Emmanuel Brachet, Yann Neuzillet, Nicolas Penel, Guilhem Roubaud, Emmanuelle Bompas, Hakim Mahammedi, Raffaelle Longo, Carole Helissey, Philippe Barthélemy, Delphine Borchiellini, Ali Hasbini, Franck Priou, Carolina Saldana, Eric Voog, Bérangère Narcisso, Sylvain Ladoire, Jean-François Berdah, Jean-Baptiste Aisenfarb, Stéphanie Foulon, Karim Fizazi
Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France. Electronic address: ., Biostatistics and Epidemiology Department, Gustave Roussy, Paris Saclay University, Villejuif, France., Institut Jean Godinot, Reims, France., ICO Paul Papin, Angers, France., Center François Baclesse, Caen, France., Department of Urology, Hospital Foch, University of Paris Saclay - UVSQ, Suresnes, France., Lille University, Lille, France; Centre Oscar Lambret, Lille, France., Department of Medical Oncology, Institut Bergonié, Bordeaux, France., ICO René Gauducheau, Saint Herblain, France., Centre Jean Perrin, Clermont Ferrand, France., Hôpital de Mercy, Metz, France., HIA Bégin, Saint Mandé, France., Strasbourg Hopital Civil, Strasbourg, France., Centre Antoine Lacassagne, Nice, France., Clinique Pasteur De Brest CFRO, Brest, France., CHD de Vendée, La Roche sur Yon, France., Hôpital Henri Mondor, Créteil, France., Centre Jean Bernard, Le Mans, France., CHU Bretonneau, Tours, France., Centre Georges François Leclerc, Dijon, France., Hôpital Privé, HPTH, Sainte Marguerite, Hyères, France., Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France., Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.