Meta-analysis of the addition of docetaxel to ADT in hormone-sensitive metastatic prostate cancer

By Matteo Stenger

Posted: 14/07/2023 10:57:00

Last update: 07/14/2023 12:02:42

In a systematic review and single patient meta-analysis reported in The Oncological Lancet, Claire L. Vale, PhDand colleagues from the STOPCAP M1 collaboration identified factors associated and unassociated with improved outcomes after the addition of docetaxel to androgen deprivation therapy (ADT) in hormone-responsive metastatic prostate cancer.

Claire L. Vale, PhD

Study details

The study involved data from 2,261 patients (98% of those randomly assigned) from three eligible studies: GETUG-AFU15, CHAARTED, and STAMPEDE. Studies were identified in literature searches through March 2023 looking for studies comparing docetaxel plus ADT vs ADT in patients with hormone-sensitive metastatic prostate cancer.

Key Findings

The median follow-up was 72 months (interquartile range = 5585 months). Based on all studies and included patients, the addition of docetaxel to ADT was associated with significant benefits in overall survival (hazard ratio [HR] = 0.79, 95% confidence interval. [CI] = 0.700.88, P < 0.0001), progression-free survival (HR = 0.70, 95% CI = 0.630.77, P < .0001) and failure-free survival (HR = 0.64, 95% CI = 0.580.71, P < .0001); 5-year absolute improvements in these outcomes with the addition of docetaxel ranged from 9% to 11%.

The benefit of adding docetaxel to ADT on progression-free survival was found to be greater with increasing clinical stage T.P = .0019 for interactions) and higher volume of metastases (P = .020 per interaction), with evidence of a treatment effect for the synchronous diagnosis of metastatic disease (P = .077 for the interaction).

In an analysis including other interactions, the docetaxel effect was independently associated with volume and clinical T-stage but not at the time of diagnosis. The greatest benefit of docetaxel was observed in patients with high volume disease and clinical stage 4 T disease for both progression-free survival (5-year absolute difference = 27%; HR = 0.36, 95% CI = 0.260, 49) and survival (5-year absolute difference = 35%; HR = 0.38, 95% CI = 0.260.53).

Addition of docetaxel among patients with low-volume metachronous disease was not associated with a benefit in progression-free survival (5-year absolute difference = 1%; HR = 0.98, 95% CI = 0.671.45) or overall survival (5-year absolute difference = 0%; HR = 1.13, 95% CI = 0.701.82).

The researchers concluded: The addition of docetaxel to hormone therapy is best suited to patients with the worst prognosis for hormone-sensitive and metastatic prostate cancer based on high disease volume and potentially primary tumor mass. There is no evidence of significant benefit for patients with low-volume metachronous disease, who should therefore be managed differently. These findings will better characterize patients most and, importantly, least likely to benefit from docetaxel, potentially changing international practice, guiding clinical decision-making, better informing treatment policy, and improving patient outcomes.

Claire L. Vale, PhDof the MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, is the corresponding author of The Oncological Lancet item.

Disclosure: The study was funded by the UK Medical Research Council and Prostate Cancer UK. For complete information on the authors of the study, visit thelancet.com.

The content of this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO) and does not necessarily reflect the views and opinions of ASCO.

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