A randomized phase 3 trial of docetaxel added to ADT plus ARTA in patients with metastatic hormone-sensitive prostate cancer (Adding Docetaxel, KCSG- GU22-24).

Abstract

TPS276 Background: The doublet regimen, which adds docetaxel or androgen receptor-targeted agent (ARTA) such as abiraterone, enzalutamide, or apalutamide to androgen deprivation therapy (ADT) has been a standard of care in metastatic hormone-sensitive prostate cancer (mHSPC). A triplet regimen, adding abiraterone or darolutamide to ADT and docetaxel, has also demonstrated efficacy. However, while the benefit of docetaxel in mHSPC has been established in doublet regimen (ADT + docetaxel), the efficacy of adding docetaxel to ADT + ARTA has not been confirmed. Notably, the addition of docetaxel to ADT has shown benefit primarily in patients with high-volume disease. Pivotal trials of triplet regimens were based on administering ADT + docetaxel to all mHSPC patients. However, docetaxel is associated with significant toxicity and a reduction in quality of life, especially among elderly prostate cancer patients. Considering the limited evidence for adding docetaxel to ADT + ARTA and considerable toxicity of docetaxel, this phase 3 study aims to evaluate the effectiveness of adding docetaxel to ADT + ARTA. Methods: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients diagnosed with de novo mHSPC and initiated on ADT and ARTA are enrolled and randomized within 16 weeks of starting ADT. Patients are randomized 1:1 to either the Adding-Docetaxel arm or the Non-Docetaxel arm. Randomizations is stratified by ARTA type (abiraterone vs. apalutamide vs. enzalutamide), ECOG PS (0-1 vs. 2), disease volume (high vs. low). The Adding-Docetaxel arm adds 6 cycles of docetaxel 75 mg/m 2 in addition to ADT + ARTA, while the Non-Docetaxel arm receives only ADT + ARTA. The primary endpoint is clinical progression-free survival (cCFS), which defined the time from randomization to progression of soft tissue lesions (per RECIST v1.1), development of cancer pain requiring opioids for more than 7 days, worsening of ECOG PS, need for a change in prostate cancer-specific therapy, need for radiotherapy or surgical treatment, or death. The study is designed to detect a hazard ratio of 0.7 for cPFS, with a significance level of 5%, power of 80%, and an anticipated drop-out rate of 10%. A total of 430 patients (215 per arm) will be enrolled. Patient recruitment began in November 2023. This trial has been registered on the Clinical Research Information Service (http://cris.nih.go.kr) under ID No. KCT0008726 (Release date: August 22, 2023). Clinical trial information: KCT0008726 .