CHAARTED Study: Conceptual Shift in Early Prostate Cancer Treatment

Analysis of results from the ECOG E3805 CHAARTED trial, published in the New England Journal of Medicine, has found that 6 cycles of chemotherapy (docetaxel) before androgen-deprivation therapy (ADT) early in the treatment of metastatic prostate cancer significantly improved overall survival than with ADT alone.

The lead author on the study, Christopher Sweeney, MBBS, from the Dana-Farber Cancer Institute, had provided trial update in an interview with The American Journal of Managed Care last year, where he said that positive results from the CHAARTED study had led to additional agents being explored in prostate cancer treatment, such as enzalutamide and abiraterone, in combination with chemotherapy.

The trial assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for 6 cycles) or ADT alone. The primary outcome of the study, designed in 2005 by the Eastern Cooperative Oncology Group, was overall survival. The trial enrolled 790 patients (median age 63 years) who were followed for a median duration of 28.9 months. Treatment with the combination of ADT and docetaxel improved overall survival by 13.6 months (median) compared with ADT alone (57.6 months versus 44.0 months, respectively). The hazard ratio (HR) for death with chemohormonal therapy was 0.61 (95% CI, 0.47 to 0.80; P<.001). The time to progression was 20.2 months for the group treated with chemohormonal therapy and 11.7 months for the group treated with ADT alone (HR, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen (PSA) level of less than 0.2 ng/ml at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group.

Based on these results, the authors conclude that docetaxel given at the time ADT was initiated for hormone-sensitive disease resulted in better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival. This was achieved despite the fact that patients administered ADT alone did receive docetaxel when their disease progressed to being castration-resistant.

The results of the CHAARTED study make it imperative that doctors speak to their newly diagnosed prostate cancer patients about using chemotherapy upfront.