Cabazitaxel activity in men with metastatic castration-resistant prostate cancer with and without DNA damage repair defects.

Cabazitaxel was shown to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone/enzalutamine and docetaxel failure, though benefit by the presence of DNA damage repair (DDR) defects is unknown.

With the advent of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) in partially overlapping indications with cabazitaxel, we aimed to determine cabazitaxel activity in men with mCRPC according to their DDR status.

This is a retrospective multicenter study that enrolled patients with mCRPC treated with cabazitaxel who had undergone DDR tumour tissue profiling. Patients with at least one deleterious germline or somatic alterations were considered DDR positive (DDR+). Each DDR + patient has been matched with a DDR negative (DDR-) from the same institution who underwent the same test. An exploratory cohort of patients found to be DDR + by liquid biopsy was also included. Prostate specific antigen (PSA) decline≥50% (PSA50), PSA progression-free survival (PFS, PSA-PFS), radiographic PFS (rPFS), clinical PFS or radiographic PFS (c/rPFS) and OS were evaluated.

Among 190 men (95 DDR+, 95 DDR-) with tissue sequencing, PSA50 was achieved with cabazitaxel in 29/92 (32%) and 33/92 (36%) in patients with DDR+ and DDR- (P = 0.64). The median rPFS was 5.33 months [95%CI 4.34-7.04] versus 5.75 months [95%CI 4.67-7.27] (P = 0.55). The median OS was 15.4 months [95%CI 12.16-26.6] and 11.5 months [95%CI 9.76-14.4] (P = 0.036), respectively. No PSA50 responses on cabazitaxel were observed in BRCA1/2 patients previously treated with PARPi (n = 10). Similar outcomes with cabazitaxel were observed in the liquid biopsy cohort (n = 63 DDR+).

Our study suggests that cabazitaxel is active in patients with mCRPC regardless of their DDR status, although its activity in men pretreated with a PARPi may be lower.

European journal of cancer (Oxford, England : 1990). 2021 Nov 02 [Epub ahead of print]

Mihaela Aldea, Laurent Lam, Emeline Orillard, Casilda Llacer Perez, Mathilde Saint-Ghislain, Gwenaelle Gravis, Aude Fléchon, Guilhem Roubaud, Philippe Barthelemy, Francesco Ricci, Frank Priou, Zoe Neviere, Mathilde Beaufils, Brigitte Laguerre, Anne-Claire Hardy, Carole Helissey, Raffaele Ratta, Delphine Borchiellini, Cedric Pobel, Florence Joly, Elena Castro, Antoine Thiery-Vuillemin, Giulia Baciarello, Karim Fizazi

Department of Cancer Medicine, Gustave Roussy, University of Paris Saclay, 114 Edouard Vaillant Street, 94805, Villejuif, France., Department of Biostatistics and Epidemiology, Gustave Roussy, 114 Edouard Vaillant Street, 94805, Villejuif, France., Department of Medical Oncology, Hôpital Jean Minjoz, 3 Boulevard Alexandre Fleming, 25000, Besançon, France., Department of Medical Oncology, Hospitales Virgen de La Victoria y Regional de Málaga, Campus de Teatinos, S/N, 29010, Málaga, Spain., Department of Medical Oncology, Centre Francois Baclesse, 3 Avenue Du Général Harris, 14000, Caen, France., Department of Medical Oncology, Institut Paoli Calmettes, 232 Boulevard de Sainte-Marguerite, 13009, Marseille, France., Department of Medical Oncology, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008, Lyon, France., Department of Medical Oncology, Institut Bergonié, 229 Cours de L'Argonne, 33000, Bordeaux, France., Department of Medical Oncology, Hôpitaux Universitaires de Strasbourg/ICANS Strasbourg, 17 Rue Albert Calmette, 67200, Strasbourg, France., Department of Medical Oncology, Institut Curie, 26 Rue D'Ulm, 75005, Paris, France., Department of Medical Oncology, Centre Hospitalier Départemental Vendée, Boulevard Stéphane Moreau, 85000, La Roche-sur-Yon, France., Department of Medical Oncology, Centre Eugène Marquis, Bataille Flandres-Dunkerque Avenue, 35000, Rennes, France., Department of Medical Oncology, Hôpital Privé des Côtes D'Armor, 10 François Jacob Street, 22190, Plérin, France., Department of Medical Oncology, Hôpital D'Instruction des Armées Begin, 69 Paris Avenue, 94160, Saint-Mandé, France., Department of Medical Oncology, Hôpital Foch, 40 Worth Street, 92150, Suresnes, France., Department of Medical Oncology, Centre Antoine Lacassagne, Université Cote D'Azur, 33 Valombrose Avenue, 06100, Nice, France., Department of Medical Oncology, Hôpital Européen Georges-Pompidou, 20 Leblanc Street, 75015, Paris, France., Department of Cancer Medicine, Gustave Roussy, University of Paris Saclay, 114 Edouard Vaillant Street, 94805, Villejuif, France. Electronic address: .

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