Long-term follow-up of a large phase III study showed that chemohormonal therapy involving docetaxel added to androgen deprivation therapy (ADT) prolongs overall survival (OS) over ADT alone in metastatic hormone-sensitive prostate cancer (mHSPC) patients with high-volume disease. Those with low-volume disease, however, did not see an OS benefit with the addition of docetaxel.
“Several therapies have been shown to improve the OS of men with castration-resistant prostate cancer (CRPC),” wrote study authors led by Christopher J. Sweeney, MBBS, of the Dana-Farber Cancer Institute in Boston. “However, most patients eventually die as a result of CRPC within a few years. Combining novel therapies with ADT at the time of initiating systemic therapy for mHSPC has emerged as a strategy to potentially delay the development of CRPC and improve quality of life and OS.”
A previous interim analysis of the CHAARTED trial showed a survival benefit with docetaxel added to ADT, but there were a low number of events at that point. The new analysis extends follow-up significantly; it includes 790 patients randomized to either ADT alone (393 patients) or in combination with docetaxel (397 patients). The results were published in the Journal of Clinical Oncology.
In the full cohort, there were 188 deaths in the ADT-plus-docetaxel group, and 211 in the ADT-alone group. The median OS was 57.6 months with docetaxel and 47.2 months without it, for a hazard ratio (HR) of 0.72 (95% CI, 0.59–0.89; P = .0018).
Specifically in patients with high-volume disease, the median OS with docetaxel was 51.2 months, compared with 34.4 months without it, for an HR of 0.63 (95% CI, 0.50–0.79; P < .001). This difference was not seen in low-volume disease, where the median OS was 63.5 months in the ADT-plus-docetaxel group and not yet reached in the ADT-alone group, for an HR of 1.04 (95% CI, 0.70–1.55; P = .086).
The time to CRPC, based on prostate-specific antigen rise or clinical progression, was 19.4 months with docetaxel and 11.7 months without it, for an HR of 0.61 (95% CI, 0.52–0.73; P < .001). This was true in both high- and low-volume disease.
The safety of the treatment was similar to that in previously published reports of docetaxel; this longer follow-up did not reveal any new safety signals with the therapy.
“The updated data confirm the benefit of docetaxel in combination with ADT for patients with mHSPC, which is clearly defined for patients with high-volume disease,” the authors concluded, adding that burden of metastases as assessed by conventional imaging can help guide patient selection for this treatment.