The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.
In, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.
These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.
Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).
“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.
However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).
In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.
Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).
There was also no significant difference in all-cause mortality between the two groups.
The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.
“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”
The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.
SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. .