Many patients 65 years or older with metastatic castration-resistant prostate cancer (mCRPC) are denied taxane chemotherapy because this treatment is considered unsuitable.
To determine whether biweekly cabazitaxel (CBZ), 16 mg/m2 (biweekly CBZ16), plus prophylactic granulocyte colony-stimulating factor (G-CSF) at each cycle reduces the risk of grade 3 or higher neutropenia and/or neutropenic complications (eg, febrile neutropenia, neutropenic infection, or sepsis) compared with triweekly CBZ, 25 mg/m2 (triweekly CBZ25), plus G-CSF (standard regimen).
A total of 196 patients 65 years or older with progressive mCRPC were enrolled in this prospective phase 3 randomized clinical trial conducted in France (18 centers) and Germany (7 centers) between May 5, 2017, and January 7, 2021. All patients had received docetaxel and at least 1 novel androgen receptor-targeted agent.
Patients were randomly assigned 1:1 to receive biweekly CBZ16 plus G-CSF and daily prednisolone (experimental group) or triweekly CBZ25 plus G-CSF and daily prednisolone (control group).
The primary end point was the occurrence of grade 3 or higher neutropenia measured at nadir and/or neutropenic complications.
Among 196 patients (97 in the triweekly CBZ25 group and 99 in the biweekly CBZ16 group), the median (IQR) age was 74.6 (70.4-79.3) years, and 181 (92.3%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median (IQR) follow-up duration was 31.3 (22.5-37.5) months. Relative dose intensities were comparable between groups (median [IQR], 92.7% [83.7%-98.9%] in the triweekly CBZ25 group vs 92.8% [87.0%-98.9%] in the biweekly CBZ16 group). The rate of grade 3 or higher neutropenia and/or neutropenic complications was significantly higher with triweekly CBZ25 vs biweekly CBZ16 (60 of 96 [62.5%] vs 5 of 98 [5.1%]; odds ratio, 0.03; 95% CI, 0.01-0.08; P < .001). Grade 3 or higher adverse events were more common with triweekly CBZ25 (70 of 96 [72.9%]) vs biweekly CBZ16 (55 of 98 [56.1%]). One patient (triweekly CBZ25 group) died of a neutropenic complication.
In this randomized clinical trial, compared with the standard regimen, biweekly CBZ16 plus G-CSF significantly reduced by 12-fold the occurrence of grade 3 or higher neutropenia and/or neutropenic complications, with comparable clinical outcomes. The findings suggest that biweekly CBZ16 regimen should be offered to patients 65 years or older with mCRPC for whom the standard regimen is unsuitable.
ClinicalTrials.gov Identifier: NCT02961257.
JAMA oncology. 2023 Oct 26 [Epub ahead of print]
Stéphane Oudard, Raffaele Ratta, Eric Voog, Philippe Barthelemy, Antoine Thiery-Vuillemin, Mostefa Bennamoun, Ali Hasbini, Kais Aldabbagh, Carolina Saldana, Emmanuel Sevin, Eric Amela, Gunhild Von Amsberg, Nadine Houede, Dominique Besson, Susan Feyerabend, Martin Boegemann, David Pfister, Martin Schostak, Olivier Huillard, Frederic Di Fiore, Amandine Quivy, Carsten Lange, Letuan Phan, Houda Belhouari, Yohann Tran, Salma Kotti, Carole Helissey
Oncology Department, Hopital European Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), University Paris Cité, Paris, France., Oncology Department, Foch Hospital, Suresnes, France., Oncology Department, Jean Bernard Center, Le Mans, France., Oncology Department, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Oncology Department, Centre Hospitalier Universitaire (CHU) Jean-Minjoz, Besançon, France., Oncology Department, Institute Mutualiste Montsouris, Paris, France., Oncology Department, Clinique Pasteur Lanroze, Brest, France., Oncology Department, Polyclinique Saint Côme, Compiègne, France., Oncology Department, Henri Mondor Hospital, Paris Est Créteil University, Therapeutic Resistance in Prostate Cancer, Créteil, France., Oncology Department, Centre Maurice Tubiana, Caen, France., Oncology Department, Centre de Cancérologie Les Dentellières, Valenciennes, France., Department of Oncology, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Oncology Department, Institut de Cancérologie du Gard, CHU de Nîmes, Montpellier University, France., Oncology Department, Centre Armoricain de Radiothérapie et d'Oncologie, Plérin, France., Studienpraxis Urologie, Studienpraxis Urologie, Nürtingen, Germany., Urology Department, Universitätsklinikum Münster, University Hospital Münster, Münster, Germany., Department of Urology, Uro-Oncology and Robot-Assisted Surgery, University Hospital of Cologne, Cologne, Germany., Department of Urology, Uro-Oncology and Robot-Assisted and Focal Therapy, University Hospital Magdeburg, Otto von Guericke University Magdeburg, Magdeburg, Germany., Oncology Department, Cochin Hospital, AP-HP, Paris, France., Uro-Digestive Oncology Unit, Rouen University Hospital, Rouen, France., Oncology Department, Saint André Hospital, Bordeaux, France., Uro-Oncologic Health Centre, Bernburg, Germany., Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, Hôpital Européen Georges Pompidou, AP-HP, Université Paris Cité, Paris, France., Oncology Department, Military Hospital Begin, Saint-Mandé, France.