The addition of docetaxel to androgen deprivation therapy did not significantly improve PSA-PFS in men with high-risk prostate cancer, rising PSA levels and no sign of metastases, according to results of a randomized phase 3 superiority trial recently published in JAMA Oncology.
“There is no standard of care for patients with hormone-sensitive prostate cancer with rising PSA levels after local therapy,” Stéphane Oudard, MD, PhD, professor of oncology and chief of the oncology clinical and translational research unit at Georges Pompidou Hospital in Paris, and colleagues wrote. “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.”
Oudard and colleagues compared ADT plus docetaxel with ADT alone among 254 men from 28 centers in France who underwent local therapy for prostate cancer, had rising PSA levels and appeared at high risk for metastatic disease.
The investigators stratified patients by previous local therapy (radical prostatectomy vs. radiotherapy) and PSA-level doubling time (6 months or less vs. more than 6 months).
Researchers randomly assigned patients 1:1 to receive one 1 year of ADT plus 70 mg/m 2 IV docetaxel every 3 weeks for up to six cycles (median age, 64 years; range, 58-70 ) or ADT alone (median age, 66 years; range, 61-71). The groups had comparable baseline characteristics , with similar percentages demonstrating at least four factors of high-risk disease.
PSA-PFS — with progression defined as a 50% or more relative increase above the nadir along with an absolute PSA increase established in a sensitivity analysis, confirmed by two more measurements at 3-week intervals — served as the primary endpoint. Secondary endpoints included PSA response, radiologic PFS, OS, safety and quality of life.
In the sensitivity analysis — in which the absolute PSA increase-defining progression ranged from 0.2 ng/mL to 2 ng/mL in 0.1 ng/mL increments — the HR did not reach statistical significance. Thus, researchers chose a 0.2-ng/mL PSA increase to define PSA progression.
Overall, 79 patients (63.2%) in the ADT-plus-docetaxel group and in 81 patients (64.8%) in the ADT-only group experienced progression .
of 30 months, researchers observed median PSA-PFS of 20.3 months (95% CI, 19- 21.6) in the combination therapy group, vs. 19.3 months (95% CI, 18.2-20.8) in the ADT-only group (HR = 0.85; 95% CI, 0.62-1.16).
All patients demonstrated a 50% or more PSA level decline from baseline. Researchers observed a complete PSA response in 91 patients (72.8%) who received ADT plus docetaxel vs. 81 patients (64.8%) who received ADT alone .
At median follow-up of 10.5 years, results showed no significant difference between groups in radiologic PFS (HR = 1.03; 95% CI, 0.74-1.43), and OS data were immature.
The most common grade 3 or grade 4 adverse events among in the ADT-plus-docetaxel group included neutropenia (48%), febrile neutropenia (8%), and thrombocytopenia (3%). Overall quality of life did not differ significantly between the groups .
The researchers noted several possible limitations of their study, including its open-label design and disputes regarding the clinical relevance of PSA-PFS as an endpoint.
Adjuvant taxane agents such as docetaxel should be used carefully in patients with high-risk prostate cancer and rising PSA, Nicholas J. Vogelzang, MD, clinical professor of medicine at University of Nevada School of Medicine and medical oncologist with Comprehensive Cancer Centers of Nevada, wrote in a related editorial.
“For patients with very poor risk who I believe have a high likelihood of early evolution to androgen receptor independence, I recommend adjuvant taxane therapy based on the meta-analysis and the STAMPEDE data,” Vogelzang wrote. “However, the marginal benefit seen in the meta-analysis, the negative results noted by Oudard [and colleagues] , and the failure of taxanes to improve survival in low-volume disease in [the] CHAARTED and GETUG-AFU 15 [trials] should make adjuvant taxane therapy a selectively considered opinion. There may be patients for whom adjuvant taxane therapy is useful — I simply do not know which patients they are. ” – by Jennifer Byrne
Disclosures: Oudard reports consultant roles with and honoraria and travel support from Astellas, Janssen and Sanofi during conduct of the study. Please see the study for all other authors’ relevant financial disclosures. Vogelzang reports personal fees from Arvinas, AstraZeneca, Janssen and Pfizer/Medication/Astellas; a vice chair role with the SWOG Genitourinary Committee; membership with the NCI Genitourinary Steering Committee; legal consulting for Novartis and stock ownership in Caris.