Gwenaelle Gravis1, Jean-Marie Boher2, Florence Joly3, Michel Soulié4, Laurence Albiges5, Franck Priou6, Igor Latorzeff7, Remy Delva8, Ivan Krakowski9, Brigitte Laguerre10, Frédéric Rolland11, Christine Théodore12, Gael Deplanque13, Jean-Marc Ferrero14, Stéphane Culine15, Loïc Mourey16, Philippe Beuzeboc17, Muriel Habibian18, Stéphane Oudard19, Karim Fizazi5. 1. Medical Oncology, Institut Paoli-Calmettes, Marseille, France. Electronic address: gravisg@ipc.unicancer.fr. 2. Biostatistics, Institut Paoli-Calmettes, Marseille, France; Aix-Marseille Université, UMR_S 912 (SESSTIM), IRD, Marseille, France; INSERM, UMR_S 912 (SESSTIM), Marseille, France. 3. Medical Oncology, Centre François Baclesse - CHU Côte de Nacre, Caen, France. 4. Urology Department, Centre Hospitalier Universitaire Rangueil, Toulouse, France. 5. Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France. 6. Medical Oncology, Centre Hospitalier Les Oudairies, La Roche-sur-Yon, France. 7. Radiotherapy Department, Clinique Pasteur, Toulouse, France. 8. Department of Medical Oncology, Centre Paul Papin, Angers, France. 9. Medical Oncology, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France. 10. Medical Oncology, Centre Eugène Marquis, Rennes, France. 11. Medical Oncology, Centre René Gauducheau, Saint-Herblain, France. 12. Medical Oncology, Hôpital Foch, Suresnes, France. 13. Medical Oncology, Groupe Hospitalier Saint Joseph, Paris, France. 14. Medical Oncology, Centre Antoine Lacassagne, Nice, France. 15. Medical Oncology, Hôpital Saint-Louis, Paris, France. 16. Institut Claudius Régaud, Toulouse, France. 17. Medical Oncology, Institut Curie, Paris, France. 18. UNICANCER, Paris, France. 19. Medical Oncology Department, Georges Pompidou Hospital and René Descartes University, Paris, France.
Abstract
BACKGROUND: The role of chemotherapy in metastatic non castrate prostate cancer (mNCPC) is debated. Survival benefits of docetaxel (D) added to androgen-deprivation therapy (ADT) were shown in the CHAARTED trial in patients with metastatic high-volume disease (HVD). OBJECTIVE: To assess the impact of metastatic burden and to update overall survival (OS) data of the GETUG-AFU15 study. DESIGN, SETTING, AND PARTICIPANTS: Randomized phase 3 trial of ADT plus D versus ADT alone in 385 mNCPC patients; median follow-up of 7 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end point was OS. Secondary end points were biochemical progression-free survival (bPFS) and radiographic progression-free survival (rPFS). Retrospective analysis was by tumor volume. RESULTS AND LIMITATIONS: After a median follow-up of 83.9 mo, median OS in the overall population was 62.1 mo (95% confidence interval [CI], 49.5-73.7) and 48.6 mo (95% CI, 40.9-60.6) for ADT plus D and ADT arms, respectively (hazard ratio [HR]: 0.88 [95% CI, 0.68-1.14]; p=0.3). Median OS in ADT plus D and ADT arms, respectively, was for HVD patients: 39.8 mo (95% CI, 28.0-53.4) versus 35.1 mo (95% CI, 29.9-43.6) (HR: 0.78 [95% CI, 0.56-1.09]; p=0.14), for low-volume disease (LVD) patients; median was not reached (NR; 95% CI, 69.5-NR) and 83.4 mo (95% CI, 61.8-NR) (HR: 1.02 [95% CI, 0.67-1.55]; p=0.9). For upfront metastatic patients, OS was 52.6 mo (95% CI, 43.3-66.8) and 41.5 mo (95% CI, 36.3-54.5), respectively (HR: 0.93 [95% CI, 0.69-1.25]; p=0.6). The bPFS (HR: 0.73 [95% CI, 0.56-0.94]; p=0.014) and rPFS (HR: 0.75 [95% CI, 0.58-0.97]; p=0.030) were significantly longer in the ADT plus D arm. Limitations included the retrospective analysis of metastatic extent and the lack of statistical power to detect a significant difference in subgroups. CONCLUSIONS: The post hoc analyses of the GETUG-AFU15 study demonstrated a nonsignificant 20% reduction in the risk of death in the HVD subgroup. Patients with LVD had no survival improvement with early D. PATIENT SUMMARY: In this study, docetaxel added to castration did not improve survival in patients with metastatic hormone-sensitive prostate cancer, partly due to methodological issues. However, early chemotherapy should be discussed with all patients, given the data of three randomized trials including GETUG-AFU15.
RCT Entities:
BACKGROUND: The role of chemotherapy in metastatic non castrate prostate cancer (mNCPC) is debated. Survival benefits of docetaxel (D) added to androgen-deprivation therapy (ADT) were shown in the CHAARTED trial in patients with metastatic high-volume disease (HVD). OBJECTIVE: To assess the impact of metastatic burden and to update overall survival (OS) data of the GETUG-AFU15 study. DESIGN, SETTING, AND PARTICIPANTS: Randomized phase 3 trial of ADT plus D versus ADT alone in 385 mNCPC patients; median follow-up of 7 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end point was OS. Secondary end points were biochemical progression-free survival (bPFS) and radiographic progression-free survival (rPFS). Retrospective analysis was by tumor volume. RESULTS AND LIMITATIONS: After a median follow-up of 83.9 mo, median OS in the overall population was 62.1 mo (95% confidence interval [CI], 49.5-73.7) and 48.6 mo (95% CI, 40.9-60.6) for ADT plus D and ADT arms, respectively (hazard ratio [HR]: 0.88 [95% CI, 0.68-1.14]; p=0.3). Median OS in ADT plus D and ADT arms, respectively, was for HVD patients: 39.8 mo (95% CI, 28.0-53.4) versus 35.1 mo (95% CI, 29.9-43.6) (HR: 0.78 [95% CI, 0.56-1.09]; p=0.14), for low-volume disease (LVD) patients; median was not reached (NR; 95% CI, 69.5-NR) and 83.4 mo (95% CI, 61.8-NR) (HR: 1.02 [95% CI, 0.67-1.55]; p=0.9). For upfront metastatic patients, OS was 52.6 mo (95% CI, 43.3-66.8) and 41.5 mo (95% CI, 36.3-54.5), respectively (HR: 0.93 [95% CI, 0.69-1.25]; p=0.6). The bPFS (HR: 0.73 [95% CI, 0.56-0.94]; p=0.014) and rPFS (HR: 0.75 [95% CI, 0.58-0.97]; p=0.030) were significantly longer in the ADT plus D arm. Limitations included the retrospective analysis of metastatic extent and the lack of statistical power to detect a significant difference in subgroups. CONCLUSIONS: The post hoc analyses of the GETUG-AFU15 study demonstrated a nonsignificant 20% reduction in the risk of death in the HVD subgroup. Patients with LVD had no survival improvement with early D. PATIENT SUMMARY: In this study, docetaxel added to castration did not improve survival in patients with metastatic hormone-sensitive prostate cancer, partly due to methodological issues. However, early chemotherapy should be discussed with all patients, given the data of three randomized trials including GETUG-AFU15.