With conflicting data, should docetaxel be used up front in newly diagnosed metastatic disease?
In 2004, docetaxel (Taxotere) received FDA approval for metastatic androgen independent prostate cancer as the first chemotherapy to extend survival. Since then, numerous studies have investigated docetaxel in earlier prostate cancer disease states.
Recently, three studies evaluated docetaxel, typically six cycles, in the early treatment of metastatic disease along with androgen deprivation. Two trials, the U.S.-based ECOG 3805 (CHAARTED) and United Kingdom-based STAMPEDE, demonstrated a significant survival advantage using initial docetaxel in hormonally naïve men with metastasis, while the French GETUG-AFU 15 trial did not. With conflicting data, should docetaxel be used up front in newly diagnosed metastatic disease?
Trial comparisons are limited by differing designs, but all used initial docetaxel with androgen deprivation. CHAARTED demonstrated a 17-month survival advantage with “high-volume disease” (>4 bony metastasis), using docetaxel with initial androgen deprivation. STAMPEDE had a complicated randomization encompassing nine different treatment arms. In STAMPEDE, the group of men who were similar to the CHARRTED participants experienced a 22-month survival advantage with early docetaxel. GETUG-AFU 15, designed similarly to CHAARTED, concluded that docetaxel should not be used as part of first-line treatment with non-castrate metastatic prostate cancer.
The CHAARTED and GETUG-AFU 15 studies have been debated as to why such similarly designed studies should have conflicting results. The sample size and statistical power was greater in CHAARTED, and it also had more men with higher volume disease and higher PSA levels than the French trial.
The 2015 update to the National Comprehensive Cancer Network prostate cancer guidelines encourages the use of upfront docetaxel with androgen deprivation for high-volume disease and discourages docetaxel use with low-volume disease, citing CHAARTED and GETUG-AFU 15. With multidisciplinary management of advanced prostate cancer, urologists and medical oncologists should use these data to jointly evaluate men presenting with metastatic, hormone-naïve prostate cancer. The bottom line: Until longer follow-up is available on low-volume disease outcomes, men with high-volume disease appear to benefit the most from this approach.