Nicholas J. Vogelzang, MD
Ten years ago, Nicholas J. Vogelzang, MD, helped design a study of docetaxel added to first-line androgen deprivation therapy (ADT) in men with newly diagnosed metastatic, hormone-sensitive prostate cancer.
He expected the combination to demonstrate a benefit over the standard treatment of hormone therapy alone, but he wasn’t prepared for the practice-changing results the trial generated: a nearly 14-month overall survival (OS) advantage in the chemotherapy-plus-ADT arm. The survival benefit was greatest for men with extensive disease spread.
The findings from the federally funded, randomized phase III study, CHAARTED (E3805),1
were reported during the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in June.
“I feel that we have changed the paradigm,” said Vogelzang, who treats patients at the Comprehensive Cancer Centers of Nevada and helps lead clinical research for the US Oncology Network, in an interview with OncLive
. “This is the first big change in the treatment of hormone-sensitive, metastatic prostate cancer since the 1940s. It’s a pretty impressive change.”
Until now, in prostate cancer, docetaxel generally has been used only in disease that progressed after treatment with ADT. Rarely, and off-label, doctors have used the chemotherapy as first-line treatment, in combination with ADT, for this patient population, Vogelzang said.
Since both drugs are available and approved for use in prostate cancer, Vogelzang expects the new combination strategy to be immediately incorporated into practice; he, for one, is already using it to treat newly diagnosed patients with high-risk disease. He said guideline changes are already in the works, and added that the strategy “should be very readily adopted by community doctors.”
Making the regimen even more accessible is the fact that its cost is expected to be relatively low, since both agents are available in generic form, Vogelzang said. “The biggest cost is probably the anti-nausea drugs, and this is not a particularly nausea-inducing regimen, so the cost is pretty modest,” he said.
Key Findings Released at ASCO
In the 8-year, National Cancer Institute (NCI)-led study, 790 men with newly diagnosed metastatic prostate cancer—two-thirds of them with high-extent disease—were randomly assigned 1:1 to receive either ADT alone or ADT with docetaxel, which was dosed at 75 mg/m2
every 3 weeks for 6 cycles within 4 months of starting ADT. After the combination cohort completed 6 courses of docetaxel, all patients continued on ADT alone. The patients were stratified so that the study arms would be balanced, said Christopher Sweeney, MBBS, a medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston who presented the study’s findings at a June 1 press briefing during the ASCO meeting.
At a median follow-up of 29 months, median OS was 44 months in the ADT group and 57.6 months in the ADT-plus-docetaxel group, or a 39% higher likelihood of survival in the combination arm at any study time point (hazard ratio 0.61, P
= .0003), Sweeney reported. The relative improvement in median OS was largest (32.2 months ADT-only versus 49.2 months combination) among the 520 patients with high-extent disease, who had either 4 or more bone metastases or liver or lung metastases, he said. Patients with low-extent disease respond better to ADT, and thus the median OS for this subset has not yet been reached.
Docetaxel also delayed disease progression. At 1 year, the proportion of patients with prostate-specific antigen (PSA) levels Ëƒ0.2 ng/mL (considered a sign of a better remission) was 11.7% in the ADT group versus 22.7% in the ADT-plus-docetaxel group, Sweeney said. The median time to clinical progression (new symptoms or metastases detected on a scan) was 19.8 months in the ADT group versus 32.7 months in the ADT-plus-docetaxel group, he said, and the measuring time to the development of CRPC—whether determined due to a rise in PSA, new symptoms, or scan—was 14.7 months in the ADT group and 20.7 months in the ADT-plus-docetaxel group.
“In prostate cancer, I am not aware of a historical study that ever offered up this magnitude of improvement in survival,” ASCO President Clifford A. Hudis, MD, chief of the Breast Cancer Medical Service at Memorial Sloan Kettering Cancer Center in New York City, said during the briefing. “Across all solid tumors, this is an almost unprecedented improvement in median survival, and I think it can be transformative for people.”