medwireNews: CHAARTED trial findings demonstrate the efficacy of docetaxel in the treatment of metastatic hormone-sensitive prostate cancer, although the overall survival (OS) benefit from its combination with androgen deprivation therapy (ADT) appears to be limited to men with high-volume disease.
After a median of 53.7 months, the median OS was 57.6 months for the 397 men who were randomly assigned to receive ADT plus up to six cycles of docetaxel 75 mg/m2 versus 47.2 months for the 393 patients given ADT alone, giving a significant hazard ratio (HR) of 0.72.
Approximately two thirds of men in both treatment arms had high-volume disease, defined as visceral metastases and/or at least four bone lesions including one site outside the vertebral column and/or pelvis, the investigators explain in the Journal of Clinical Oncology.
Subgroup analysis of high-volume patients confirmed that ADT plus docetaxel was associated with a significant 16.8 months gain in OS compared with ADT alone, with a median OS of 51.2 versus 34.4 months and a HR of 0.63.
But no such OS benefit with ADT plus docetaxel was found for the low-volume patients, with a median OS of 63.5 months versus not reached for the ADT only treatment arm, report Christopher Sweeney, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and co-authors.
They emphasize that their findings should be viewed in light of the LATITUDE and STAMPEDE findings, which demonstrated a similar sized OS benefit from the addition of abiraterone acetate to ADT for men with high-volume disease.
“Notably, the predominant population accrued to these studies had de novo metastatic disease”, the team comments.
“The future question will be whether to add docetaxel to ADT and newer [androgen receptor]-targeting agents such [as] abiraterone (or enzalutamide if proven to confer OS benefit in the [metastatic hormone-sensitive prostate cancer] setting).”
They continue: “Fortunately, three studies have or have nearly completed accrual and are stratified by docetaxel use and will allow an analysis of ADT plus docetaxel with or without abiraterone, enzalutamide, or apalutamide.”
Nevertheless, the team concludes that while metastatic burden can help identify patients who will benefit from docetaxel, “additional studies should focus on identifying more accurate biomarkers and gaining a better understanding of the underlying mechanisms of resistance to ADT and the biologic basis for [androgen receptor] targeting and cytotoxics in prostate cancer.”
Kyriakopoulos CE, Chen Y-H, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: Long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol; Advance online publication 31 January 2018. DOI: 10.1200/JCO.2017.75.3657
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