New horizons in the management of hormone-naïve prostate cancer
“In 2015, the CHAARTED and STAMPEDE studies showed that adding six cycles of docetaxel to androgen deprivation therapy [ADT] in men with hormone-naïve, high-risk, metastatic hormone-sensitive PC [mHSPC] yielded remarkable overall survival [OS] and failure-free survival [FFS] benefits,” said Attard. “The addition of docetaxel improved median OS by 13.4 and 10.0 months in the CHAARTED and STAMPEDE trials, respectively, suggesting that docetaxel should be considered for newly diagnosed mHSPC in addition to ADT.” [N Engl J Med 2015;373:737-746; Lancet 2016;387: 1163-1177]
In both studies, the OS benefit of docetaxel was more pronounced in patients with high-volume metastatic disease (M1) than those with no distant metastasis (M0). “This was confirmed in a meta-analysis where the M0 group had a solid 8 percent absolute reduction in the risk of progression, but only a trend towards improved survival with docetaxel,” he noted. “In contrast, M1 patients had a 10 percent absolute improvement in OS and a 15 percent absolute improvement in FFS.” [Lancet Oncol 2016;17:243-256]
This year, data from the STAMPEDE and LATITUDE trials reported at the American Society of Clinical Oncology 2017 Annual Meeting demonstrated that adding abiraterone to ADT in men with newly diagnosed, locally advanced or metastatic PC significantly improved OS and doubled the time to disease progression.
In the abiraterone arm of STAMPEDE, more than 1,900 patients were randomized 1:1 to receive ADT alone or ADT plus abiraterone acetate and prednisolone. “There was a 37 percent improvement in OS, and a 71 percent improvement in time to treatment failure in the abiraterone arm,” reported Attard. “The data showed no heterogeneity by metastatic status, demonstrating an equivalent benefit in M0 and M1 patients.” [N Engl J Med 2017;377:338-351]
In the LATITUDE trial, 1,199 patients with newly diagnosed, high-risk mHSPC were randomized to receive ADT plus placebo or ADT plus abiraterone and prednisolone. Median OS was 34.7 months in the control arm, and not yet reached in the abiraterone arm. “This represents a 38 percent reduction in mortality with abiraterone, with the benefit evident in all subgroups,” he pointed out. “Abiraterone also reduced the risk of disease progression by 53 percent, and showed significant benefits in secondary endpoints such as time to next skeletal-related event, time to pain progression, time to prostate-specific antigen progression, and time to subsequent therapy for PC.” [N Engl J Med 2017;377:352-360]
“Given the solid data from those trials, docetaxel or abiraterone should become standard of care for men with M1 PC starting ADT. In my view, docetaxel or abiraterone should also be considered for patients with M0 disease,” suggested Attard. “However, questions such as the choice between abiraterone vs docetaxel, and which patients would benefit most from these therapies still remain.”