CHICAGO, IL—Upfront standard androgen deprivation therapy (ADT) plus six cycles of docetaxel significantly improves overall survival (OS) compared with ADT alone in men with metastatic hormone-sensitive prostate cancer, a phase 3 trial concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
This represents an appropriate option for men suitable for docetaxel therapy, said Christopher Sweeney, MBBS, medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, MA. “The benefit in patients with a high volume of metastases is clear and justifies the treatment burden,” he emphasized.
However, longer follow-up is required for patients with low volume metastatic disease.
Opening his presentation with a quick review of the history of hormone-sensitive metastatic prostate cancer, Dr. Sweeney noted that in the 1940s, testosterone suppression resulted in prostate cancer regression; however, it was not until a decade ago that docetaxel was shown to confer an OS benefit, of approximately 2 months.
Between July 2006 and November 2012, the CHAARTED (ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) E3805 study randomly assigned 790 men to ADT alone (n = 393) or ADT plus docetaxel 75 mg/m2 every 3 weeks for six cycles (n = 397) within 4 months of starting ADT.
Patients were stratified by high volume (visceral metastases and/or four or more bone metastases) versus low volume disease; antiandrogen use beyond 30 days; age 70 years or older versus younger than 70 years; Eastern Cooperative Oncology Group (ECOG) performance status 0-1 versus 2; prior adjuvant ADT less than 12 months versus 12 months or longer; and whether they were taking a Food and Drug Administration–approved drug for delaying skeletal-related events.
The primary endpoint was OS, with the projected median OS for ADT alone of 33 months for men with high volume disease and 67 months for low volume disease.
Median age was 64 years (range, 36 to 88 years) in the ADT-plus-docetaxel arm and 63 years (range, 39-91 years) in the ADT-alone arm; 98.5% and 98.7% had an ECOG PS of 0 or 1, respectively; 88.7% and 87.3% were Caucasian; and 20.4% and 18.6%, prior prostatectomy. Of those with high volume disease, 63.9% were on ADT and 66.2% were on ADT plus docetaxel.
Median OS was 44 months in the ADT-alone arm versus 57.6 months in the ADT-plus-docetaxel arm (hazard ratio [HR], 0.61; 95% CI: 0.47-0.80, P = 0.0003). In the ADT-plus-docetaxel arm, there were 101 deaths, 84 to prostate cancer, one due to protocol treatment, eight to other causes, and eight, unknown. In the ADT-alone arm, there were 136 deaths, 112 due to prostate cancer, 11 due to other causes, 11 unknown, and two missing.
Median OS by extent of metastatic disease at start of ADT was 32.2 months in the ADT-alone arm versus 49.2 months in the ADT-plus-docetaxel arm (HR, 0.60; 95% CI: 0.45-0.81; P = 0.0006), representing “a 17-month improvement in median OS” with ADT plus docetaxel, Dr. Sweeney said. For those with low volume disease, median OS was not reached in either arm and follow-up continues.