Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial

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.