ASCO 2014: Adding Docetaxel to Androgen-Deprivation Therapy Significantly Improves Survival in Hormone-Sensitive Prostate Cancer
The addition of docetaxel to androgen-deprivation therapy extended survival for men with newly diagnosed hormone-sensitive prostate cancer by more than 13 months in the National Cancer Institute–led phase III E3805 study. The survival benefit was even greater for men with high-volume disease.
“This is the first study to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer. The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy,” noted the lead study author Christopher Sweeney, MBBS, medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston. Dr. Sweeney reported the study results at the 2014 ASCO Annual Meeting in Chicago (Abstract LBA2).
Most Patients Had High-Volume Disease
Androgen-deprivation therapy alone is the standard first-line treatment for hormone-sensitive prostate cancer, with chemotherapy typically initiated only after the disease progresses despite hormone therapy. In the current study, 790 men with newly diagnosed metastatic prostate cancer were randomly assigned to receive either androgen-deprivation therapy alone or with docetaxel dosed at 75 mg/m2 every 3 weeks for a maximum of six cycles within 4 months of starting androgen-deprivation therapy.
The median age of patients was 63 years (range, 36–91). Approximately two-thirds of patients had high-volume disease, with either extensive bone metastases or visceral disease.
Delayed Disease Progression
At a median follow-up of 29 months, there were 136 deaths in the androgen-deprivation therapy alone group vs 101 in the androgen-deprivation therapy plus docetaxel group. The median overall survival was 44 months in the androgen-deprivation therapy group and increased to 57.6 months in the androgen-deprivation therapy plus docetaxel group.
Among the 520 patients with high-volume disease, the relative improvement in median overall survival was even greater (32.2 vs 49.2 months). The median overall survival for the subset with low-volume disease has not yet been reached.
Docetaxel also delayed disease progression, as assessed by either prostate-specific antigen (PSA) rise or appearance of new metastases or symptom worsening. At 1 year, the proportion of patients with PSA levels < 0.2 ng/mL was 11.7% in the androgen-deprivation therapy group vs 22.7% in the androgen-deprivation therapy plus docetaxel group (P < .0001). The median time to clinical progression, as evidenced by new symptoms or metastases detected on a scan, was 19.8 months in the androgen-deprivation therapy alone group vs 32.7 months in the androgen-deprivation therapy plus docetaxel group (P < .0001).
Of the 174 patients in the androgen-deprivation therapy only group who had disease progression, 129 patients received docetaxel. “So three-quarters of the patients actually got the subsequent therapy that was used upfront in the combination,” Dr. Sweeney reported at the ASCO plenary press briefing. Among those who received the combination upfront, 145 had disease progression and 49 received additional docetaxel.
Survival Benefit Justifies Treatment Burden
“Very importantly, when we are using a cytotoxic that does have a side-effect profile, we need to qualify and quantify the toxicities,” Dr. Sweeney stressed. Neutropenic fever occurred in 6% of patients receiving docetaxel. “There was a significant impact on nerve function, 1% sensory and 1% motor,” Dr. Sweeney added. “One of the 397 patients who received early docetaxel died due to treatment.”
The certainty of the data showing overall survival benefit of upfront chemohormonal therapy for men with metastatic prostate cancer “is strong for patients with high-volume disease and clearly justifies the treatment burden” for those suitable for docetaxel therapy or “chemo-fit,” Dr. Sweeney stated. “Some patients are too frail for chemotherapy,” he noted.
“This is one of the biggest improvements in survival we have seen in a trial involving patients with an adult metastatic solid tumor,” Dr. Sweeney said. “Longer follow-up is required to get more certainty on the benefit for patients with low-volume metastatic disease.”
Lingering Issues
“Across all of solid tumors, this is an almost unprecedented improvement in median survival,” stated ASCO Immediate Past President Clifford A. Hudis, MD, FACP, Chief of the Breast Cancer Medicine Service at Memorial Sloan Kettering Cancer Center, New York, who served as moderator of the ASCO plenary press briefing. These findings “could be transformative,” he said, while noting that toxicity remains an issue.
“The investigators have adequately shown that high-volume patients with castration-sensitive metastatic disease do benefit from upfront docetaxel, and it does appears to confer a survival benefit that is superior to docetaxel given at metastatic castration-resistant disease,” commented Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, New York, following Dr. Sweeney’s presentation at the Plenary Session. “But there are insufficient data at this time, after 29 months of median follow-up,” Dr. Morris added, “to recommend that low-volume patients with castration-sensitive disease undergo chemotherapy and we do need to optimize the distinction between those who benefit from chemotherapy and those who don’t.”
This research was supported by the National Cancer Institute, National Institutes of Health. Dr. Sweeney reported a consultant or advisory role with Astellas Pharma, BIND Biosciences, Bionomics, Exelixis, Genentech, Janssen Pharmaceuticals, Roche, and Sanofi. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
