As in other solid tumors, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis than patients with extensive metastatic disease. Stereotactic body radiotherapy (SBRT) is now considered an option in this population.Programmed death-1 (PD-1) and its ligands (PD-L1) are targeted by immune checkpoint inhibitors. Preclinical studies have shown that the tumor immune microenvironment changes when combining radiotherapy with immunotherapy, especially with hypofractionated radiotherapy.The oligometastatic setting appears to be the most relevant clinical situation for evaluating the immune response generated by radiotherapy and immune checkpoint inhibitors in patients with an intact immune system.We hypothesize that durvalumab will enhance the immune response following SBRT targeting oligometastatic lesions. Our purpose is to demonstrate, via a randomized 2:1 phase II trial, that SBRT (3 fractions) with durvalumab in oligometastatic hormone-sensitive prostate cancer patients would improve progression-free survival in patients with prostate cancer with up to 5 metastases compared to patients who exclusively received SBRT.
This is a multicentric randomized phase II study in French academic hospitals. Patients with prostate cancer and up to 5 metastases (lymph node and/or bone) were randomized into a 2:1 ratio between Arm A (experimental group), corresponding to durvalumab and SBRT to the metastases, and Arm B (control group), corresponding to SBRT alone to the metastases. The study aims to accrue a total of 96 patients within 3 years. The primary endpoint is two-year progression-free survival and secondary endpoints include androgen deprivation therapy-free survival, quality of life, toxicity, prostate cancer specific survival, overall survival, and immune response.
The expected benefit for the patients in the experimental arm is longer life expectancy with acceptable toxicity. We also expect our study to provide data for better understanding the synergy between immunotherapy and radiotherapy in oligometastatic prostate cancer.
Clinical and translational radiation oncology. 2023 Mar 08*** epublish ***
Maximilien Rogé, Yoann Pointreau, Paul Sargos, Emmanuel Meyer, Ulrike Schick, Ali Hasbini, Emmanuel Rio, Guillaume Bera, Amandine Ruffier, Magali Quivrin, Mathieu Chasseray, Igor Latorzeff, Etienne Martin, Valentine Guimas, Pascal Pommier, Thomas Leroy, Philippe Ronchin, Alexis Lepinoy, Audrey Grand, Lysian Cartier, Ossama Didas, Fabrice Denis, Vincent Libois, Audrey Blanc-Lapierre, Stéphane Supiot
Department of Radiation Oncology, Centre Henri Becquerel, 1 rue d'Amiens, 76000 Rouen, France., Department of Radiation Oncology, Centre Jean Bernard, 9 Rue Beauverger, 72100 Le Mans, France., Department of Radiation Oncology, Institut Bergonié, 229 Cr de l'Argonne, 33076 Bordeaux, France., Department of Radiation Oncology, Centre François Baclesse, 3 Av. du General Harris, 14000 Caen, France., Department of Radiation Oncology, University Hospital Morvan, 2 avenue Foch, 29200 Brest, France., Department of Radiation Oncology, Clinique Pasteur, 32 Rue Auguste Kervern, 29200 Brest, France., Department of Radiation Oncology, Centre Hospitalier de Bretagne Sud, 5 avenue de Choiseul, 56322 Lorient, France., Department of Radiation Oncology, Georges-François Leclerc Cancer Centre-UNICANCER, 1 Rue Professeur Marion, 21000 Dijon, France., Department of Radiation Oncology, Oncorad Clinique Pasteur, 1, rue de la Petite Vitesse, 31 000 Toulouse, France., Department of Radiation Oncology, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008 Lyon, France., Department of Radiation Oncology, Clinique des Dentellières, 8 av Vauban, 59300 Valenciennes, France., Department of Radiation Oncology, Centre Azureen de Cancerologie, 1 Place Docteur Jean Luc Broquerie, 06250 Mougins, France., Department of Radiation Oncology, Bourgogne Institute of Oncology, 18 Cr General de Gaulle, 21000 Dijon, France., Department of Radiation Oncology Center Hospitalier Lyon Sud, 165 Chem. du Grand Revoyet, 69495 Pierre-Bénite, France., Department of Radiation Oncology, Institut Sainte Catherine, 250 Chem. de Baigne Pieds, 84918 Avignon, France., Department of Radiation Oncology, Hôpital Bretonneau, CHU de Tours, 2, boulevard Tonnellé, 37044 Tours, France., Department of Biostatistics, Institut de Cancérologie de l'Ouest, Bd Professeur Jacques Monod, 44800 Saint Herblain, France.