The upfront addition of docetaxel to androgen deprivation therapy (ADT) adds more than 1 year to overall survival compared with ADT alone in men with newly diagnosed hormone-sensitive prostate cancer, according to findings from a phase 3 study funded by the National Cancer Institute.
The survival benefit was even greater for the subset of men with high-volume disease, reported Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston.
“The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy,” he said. Docetaxel is typically initiated only after disease progression despite ADT. The study randomized 790 men with newly diagnosed metastatic prostate cancer to either ADT alone or to ADT with docetaxel over 18 weeks. Approximately 66% of patients had high-volume disease.
At a median follow-up of 29 months, 136 deaths occurred in the ADT-alone group compared with 101 in the group receiving ADT plus docetaxel. Overall survival was improved by 13 months with upfront docetaxel: 44 months in the ADT group versus 57.6 months in the group receiving ADT plus docetaxel, for a relative improvement of 39% (P = .003).
In men with high-volume disease, the median overall survival was 49.2 months with docetaxel plus ADT compared with 32.2 months with ADT, corresponding to a 40% reduction in the risk of death with the addition of docetaxel (P = .006). In men with low-volume disease, the median overall survival had not been reached at the time of the analysis.
Docetaxel also delayed disease progression, assessed by either a rise in the level of prostate-specific antigen (PSA) or the appearance of new metastases or symptom worsening. At 1 year, the proportion of patients with PSA levels of <0.2 ng/mL was 11.7% in the ADT group versus 22.7% in the group receiving ADT plus docetaxel. The median time to clinical progression was 19.8 months in the ADT group compared with 32.7 months in the group receiving ADT plus docetaxel (P <.001).
Median time to castration-resistant prostate cancer was also significantly improved with the addition of docetaxel compared with ADT alone (20.7 months vs 14.7 months; P <.001).
At disease progression, 129 (approximately 75%) of the 174 patients in the ADT-alone arm subsequently received docetaxel, Dr Sweeney said.
Adverse effects in the men assigned to docetaxel included febrile neutropenia (6%) and significant effects on sensory nerves (1%) and on motor nerves (1%).
Immediate past president of ASCO, Clifford A. Hudis, MD, remarked, “In prostate cancer, I’m not aware of a historical study that ever offered up this magnitude of improvement in survival. Across all solid tumors, this is all almost unprecedented improvement in median survival.”
Michael J. Morris, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, said that the study results bear on the ongoing dialogue regarding cost versus value in cancer care.
“Docetaxel is going to cost less than our newer therapies,” Dr Morris said. “I estimate that using docetaxel in castration-resistant prostate cancer gains 81 days of life for $15,000 of drug costs at wholesale prices. If docetaxel is applied in castration-sensitive disease, it gains 476 days of life at a cost of $9000 for 6 cycles.”