EAU 2019: Conclusions from Recent Oncology Meetings Regarding: Castration-Resistant Prostate Cancer

Barcelona, Spain (UroToday.com) In this session, Dr. Evans presented a review of some of the most important studies in the castrate-resistant prostate cancer space published in the past year. First, from ESMO 2018, in a phase 3 randomized controlled trial, radium 223 with abiraterone (ERA 223) did not demonstrate improved symptomatic skeletal-related event-free or overall survival compared to abiraterone with placebo. Clinical fractures were more common in the abiraterone and radium group. Based on the data from the study, the use of radium 223 in combination with abiraterone was not recommended.

In the poor prognostic mCRPC patients, a phase 2 study was presented at ESMO 2018 comparing cabazitaxel to abiraterone or enzalutamide, with a primary outcome of clinical benefit, defined as a PSA decline >50%, complete or partial response or stable disease >12 months. There was a higher clinical benefit rate for cabazitaxel compared to abiraterone or enzalutamide for this cohort, however, survival rates were not different. Furthermore, baseline and on-treatment change in ctDNA was prognostic.

Checkmate 650, an open label phase 2 study, compared nivolumab 1mg/kg + ipilimumab 3mg/kg then continued nivolumbab 480mg Q4w for asymptomatic or minimally symptomatic patients who progressed after 1 second generation hormone therapy (without previous chemotherapy) or who had progressed after chemotherapy in the mCRPC setting. Survival benefit was observed regardless of prior chemotherapy exposure, but appeared more pronounced in patients who had not received prior chemotherapy. Preliminary data suggested that biomarkers may have a role in identifying patients with mCRPC likely to respond (TMB).

The SPARTAN trial, a phase 3 randomized placebo controlled trial, analyzed progression free survival for apalutamide + ADT versus placebo + ADT in high risk non-metastatic CRPC patients. Treatment with apalutamide prior to the development of metastasis resulted in an improvement of progression free survival, with a 50% reduction in risk of secondary progression or death, suggesting that early therapy may be more effective than waiting until metastasis develop.

Finally, ARAMIS trial evaluated the efficacy and safety of darolutamide in non-metastatic CRPC, which was also presented at GU ASCO 2019. Darolutamide is a next generation androgen receptor antagonist, with low blood brain barrier penetration, theorized to have less CNS toxicity and improved tolerability. Patients with non-metastatic CRPC and a rapid doubling time were randomized to darolutamide + ADT versus placebo + ADT, demonstrating a 59% risk reduction of distant metastasis or death.

Presented by: Christopher P. Evans, M.D., FACS, Department of Urologic Surgery, University of California-Davis, Sacramento, California

Written by: David B. Cahn, DO, MBS@dbcahn Fox Chase Cancer Center at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.

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