Researchers tested the combination of docetaxel and ADT in a phase III randomized trial of patients with high-risk nonmetastatic prostate cancer.
Adding docetaxel to androgen deprivation therapy (ADT) failed to improve prostate-specific antigen progression-free survival (PSA-PFS) in a phase III randomized trial of patients with high-risk nonmetastatic prostate cancer.
“There is no standard of care for patients with hormone-sensitive prostate cancer with rising PSA levels after local therapy,” wrote study authors led by StÃ©phane Oudard, MD, PhD, of the HÃ´pital EuropÃ©en Georges Pompidou in Paris. “Many clinicians initiate ADT, but only once metastatic disease has developed, and, to our knowledge, no formal clinical trials have examined the benefits of ADT in patients with biochemical relapse only.”
The new study included 254 patients randomized to receive either ADT for 1 year plus docetaxel for 6 cycles or ADT alone. All patients had undergone primary local therapy for prostate cancer, and were experiencing rising PSA levels and were considered at high risk for metastatic disease. Patient characteristics were well balanced between the two groups; more than 90% of both groups had an ECOG performance status score of 0. The results of the study were published in JAMA Oncology.
After a median follow-up of 30.0 months, 79 patients in the group who received ADT plus docetaxel experienced a PSA progression (63.2%), compared with 81 patients in the ADT-alone arm (64.8%). The median PSA-PFS was 20.3 months with the combination, and 19.3 months with ADT alone, for a hazard ratio (HR) of 0.85 (95% CI, 0.62–1.16; P = .31).
All patients in both study arms experienced at least a 50% decline in PSA level from baseline. A complete PSA response, defined as a 50% or more decline in PSA and an absolute PSA level of 0.1 ng/mL or lower, was observed in 72.8% of the combination group and in 64.8% of the ADT monotherapy group.
The median follow-up time for assessment of radiologic PFS and overall survival was 10.5 years. The median time to radiologic PFS was 8.9 years with ADT plus docetaxel and 9.0 years with ADT alone, for an HR of 1.03 (95% CI, 0.74–1.43; P = .88). The median overall survival was not reached in the study; 40 patients died in the combination group (32.0%) and 46 died in the ADT-alone group (36.8%). There was no difference in an exploratory analysis of time to metastatic progression.
“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” the authors concluded. “Significant improvements in metastasis-free survival and a reduction in prostate cancer deaths in high-risk, nonmetastatic, castration-resistant prostate cancer have recently been reported with new potent amides blocking the androgen receptor pathway.”
In an accompanying editorial, Nicholas J. Vogelzang, MD, of the Comprehensive Cancer Centers of Nevada in Las Vegas, wrote that the negative results are disappointing. “We now know that the optimism of 15 to 20 years ago for adjuvant chemotherapy in this population (based on the benefits of adjuvant chemotherapy in breast cancer) was unfounded because of the differing biologic characteristics of prostate and breast cancer.”
Vogelzang said that based on this and other studies, he recommends ADT for all high-risk patients, and adjuvant taxane therapy in patients with particularly poor risk profiles (node positivity, detectable PSA after radical prostatectomy, young age). However, these and other results, he noted, “should make adjuvant taxane therapy a selectively considered option.”