medwireNews: Supplementing androgen deprivation therapy (ADT) with docetaxel does not appear to improve the outcomes of men with high-risk nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) levels after treatment, indicate phase III trial findings.
After a median follow-up of 30.0 months, median PSA–progression-free survival (PFS) was 20.3 months for the 125 participants who after primary local therapy were randomly assigned to receive six cycles of docetaxel 70 mg/m2 every 3 weeks alongside ADT, and was 19.3 months for their 125 counterparts given ADT alone, when PSA progression was defined as an increase of 0.2 ng/mL.
This gave a nonsignificant hazard ratio (HR) for PSA progression of 0.85 in favor of docetaxel, with a similar, but again nonsignificant, magnitude of risk reduction observed across most subgroups, including in patients who initially underwent prostatectomy or radiotherapy and those with a PSA doubling time of up to 6 months or more than 6 months, report the researchers.
Radiologic PFS was also comparable between the trial arms, at a median of 8.9 years for the docetaxel plus ADT group and 9.0 years for the ADT alone group, and the overall survival data were not mature at the time of analysis, which was conducted at a median follow-up of 10.5 years.
Stéphane Oudard (Georges Pompidou Hospital, Paris, France) and co-investigators therefore conclude in JAMA Oncology that the “[a]ddition of docetaxel to androgen-deprivation therapy seems to be unwarranted in patients with high-risk prostate cancer without metastases in the absence of better predictors of risk for metastatic disease.”
However, speaking to medwireNews, Nicholas James (University of Birmingham, UK) – who is chief investigator of the large UK-based STAMPEDE trial which showed a significant benefit with the addition of docetaxel in a similar population – pointed out that “this trial only has 125 patients randomised to each arm so is very underpowered if it is aiming to detect the size of benefit seen in STAMPEDE and related trials like CHAARTED.”
“Secondly, for the primary outcome of PSA–PFS, the point estimate of the hazard ratio is 0.85 (a 15% improvement) and all the subgroups are consistent with this HR. This estimate is consistent with the benefit of 0.75 (ie, a 25% gain) seen in STAMPEDE and the meta-analysis we published with it,” he added.
“In short, this is an underpowered trial, but the results are consistent with the benefit seen in STAMPEDE and CHAARTED,” James noted.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
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