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.

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.