In a systematic review and individual patient meta-analysis reported in The Lancet Oncology, Claire L. Vale, PhD, and colleagues in the STOPCAP M1 collaboration identified factors associated and not associated with improved outcomes after the addition of docetaxel to androgen-deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer.
Claire L. Vale, PhD
Study Details
The study involved data from 2,261 patients (98% of those randomly assigned) from three eligible trials: GETUG-AFU15, CHAARTED, and STAMPEDE. The trials were identified in literature searches through March 2023 looking for research that compared docetaxel plus ADT vs ADT in patients with metastatic hormone-sensitive prostate cancer.
Key Findings
Median follow-up was 72 months (interquartile range = 55–85 months). Based on all included trials and patients, the addition of docetaxel to ADT was associated with significant benefits in overall survival (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.70–0.88, P < .0001), progression-free survival (HR = 0.70, 95% CI = 0.63–0.77, P < .0001), and failure-free survival (HR = 0.64, 95% CI = 0.58–0.71, P < .0001); the 5-year absolute improvements in these outcomes with the addition of docetaxel ranged from 9% to 11%.
The benefit of the addition of docetaxel to ADT on progression-free survival was found to be greater with increasing clinical T stage (P = .0019 for interactions) and higher volume of metastases (P = .020 for interaction), with evidence of a treatment effect for synchronous diagnosis of metastatic disease (P = .077 for interaction).
In an analysis including other interactions, the effect of docetaxel was independently associated with volume and clinical T stage but not timing of diagnosis. The greatest benefit of docetaxel was observed in patients with high-volume disease and clinical T stage 4 disease for both progression-free survival (absolute 5-year difference = 27%; HR = 0.36, 95% CI = 0.26–0.49) and overall survival (absolute 5-year difference = 35%; HR = 0.38, 95% CI = 0.26–0.53).
The addition of docetaxel among patients with low-volume, metachronous disease was not associated with a benefit in progression-free survival (absolute 5-year difference = –1%; HR = 0.98, 95% CI = 0.67–1.45) or overall survival (absolute 5-year difference = 0%; HR = 1.13, 95% CI = 0.70–1.82).
The investigators concluded: “The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumor. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterize patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision-making, better informing treatment policy, and improving patient outcomes.”
Claire L. Vale, PhD, of the MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the UK Medical Research Council and Prostate Cancer UK. For full disclosures of the study authors, visit thelancet.com.
