At a plenary session at the ASCO Annual Meeting, Christopher Sweeney, MBBS, presented the results of the Eastern Cooperative Oncology Group (ECOG) phase III randomized CHAARTED trial, which looked at whether the addition of upfront chemotherapy to hormonal therapy improved overall survival in patients with hormone-sensitive metastatic prostate cancer. The study was based on the fact that docetaxel is known to improve overall survival in metastatic prostate cancer patients who have progressed on androgen deprivation therapy, and it addressed the question of whether upfront docetaxel also confers an overall survival advantage for these patients.
The CHAARTED trial enrolled 790 patients, diagnosed with hormone-sensitive metastatic prostate cancer between July 2006 and November 2012, who were known to have adequate organ function in order to undergo treatment with docetaxel chemotherapy. If the patients had already been on androgen deprivation therapy, it had to be for 24 months or less, and they could not have progressed within 12 months. Patients were stratified by age (younger or older than age 70); ECOG performance status of 0–1 vs 2; whether adjuvant androgen deprivation therapy had been administered within 12 months; and high- vs low-volume disease, with high-volume disease being defined as having the presence of visceral metastases and/or four or more bone metastases.
There was 1:1 randomization to androgen deprivation therapy alone vs androgen deprivation therapy with the addition of docetaxel at a dose of 75 mg/m2 every 3 weeks for 6 cycles that had to be started within 4 months of the inception of androgen deprivation therapy. The primary endpoint was overall survival, and the study was designed to detect a 33% improvement in overall survival.
The results reported were in favor of adding docetaxel to androgen deprivation therapy in men with hormone-sensitive metastatic prostate cancer. It was found that androgen deprivation therapy plus docetaxel resulted in a median overall survival of 57.6 months (hazard ratio = 0.61; P = .0003) compared with 44 months in the androgen deprivation therapy–alone arm. In stratifying the patients according to high-volume vs low-volume disease, the benefit for docetaxel therapy was found to be more apparent in the high-volume metastatic group vs the low-volume metastatic group, although longer follow-up will be required to further evaluate the benefit for low-volume disease.
As commented on in the plenary discussion, there is a need for the development of better models on who the “high-” and “low-” volume disease groups should include. It was shown, for example, that a patient with four small bone metastases in their ribs would be considered to have high-volume disease and thus would be recommended to receive docetaxel based on the overall survival benefit in this study. However, a patient with one large bony metastatic lesion in their hip would not qualify as having high-volume disease based on the authors’ definition; however, he or she may benefit from docetaxel despite their metastases being classified as low-volume.
Overall, the CHAARTED trial is an important, positive study that may change our management of patients with hormone-sensitive metastatic prostate cancer.