The LATITUDE study [4], a double blind, placebo controlled phase 3 trial, conducted at 235 sites in 34 countries in Europe, Asia- Pacific, Latin America, and Canada, was designed and fully enrolled prior to publication of CHAARTED/STAMPEDE results. This trial randomized de novo MCSPC patients to either ADT + Abiraterone or ADT + placebo. The primary endpoints included overall survival and progression free survival. The study demonstrated that the overall survival rate at 3 years was 66% for ADT + Abiraterone, compared to 49% in ADT + placebo. Secondary exploratory endpoints also demonstrated that the Abiraterone arm also had better time to pain progression, time to PSA progression, time to next symptomatic skeletal event, time to chemotherapy, and time to subsequent prostate cancer therapy.
The STAMPEDE, a multigroup, multistage trial also analyzed patients scheduled for long term ADT, including newly diagnosed M1 or N+ situations, and randomized them to either standard of care plus Abiraterone, or standard of care alone. The results demonstrated a hazard ratio (HR) of 0.63 for overall survival in favor of the abiraterone arm. Importantly, there was no difference in treatment related deaths between the two arms. However, twice as many patients discontinued the treatment due to toxicity in the combination arms in STAMPEDE (20%) compared to LATITUDE (12%).
A recently published study in the Annals of Oncology [5] is a randomized comparative analysis of two new treatment standards (ADT + abiraterone and ADT + docetaxel) for hormone naïve prostate cancer patients, showing that there was no difference in overall or prostate cancer specific survival. I
In conclusion, addition of abiraterone to ADT has led to significantly improved overall survival with a 38% reduction in the risk of death, and significantly prolonged progression free survival, and all secondary end points. These findings indicate that the addition of abiraterone to ADT can be considered the new standard of care for patients with newly diagnosed MCSPC. Due to these impressive results, the recent EAU guidelines have incorporated these findings and strongly advocate for the usage of ADT + Abiraterone, or ADT + docetaxel for all patients presenting with metastasis, who are fit enough to withstand this treatment protocol.
Figure 1: ADT + docetaxel is the new standard of care for men with metastatic castrate sensitive prostate cancer and high burden of metastatic disease
Speaker: D. Tilki, Hamburg (DE), N. Mottet, Saint-Étienne (FR)
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark
References:
[1] James N et al. Lancet. 2016; 387:1163-1177
[2] Sweeney C, et al. N eng J Med 2015; 373: 737-746
[3] Gravis G, et al. Eur Urol 2016: 70:256-262
[4] Fizazi K, N Eng J Med 2017; 377 (4): 352-360
[5] Sydes et al. Annals of Oncology, 2018