AUA 2017: Combination or Sequential Therapy for Castration-Resistant Prostate Cancer

Boston, MA ( Dr. Chris Sweeney concluded an excellent ‘Best of Boston’ session at the 2017 American Urological Association Annual Meeting by discussing a very important topic in the setting of advanced disease, namely what combination or sequential therapy should we be considering for castration-resistant prostate cancer (CRPC).

The speaker began his talk by noting that we have level-1 evidence of a single agent with overall survival benefit after another agent, namely (i) cabazitaxel after docetaxel, (ii) abiraterone after docetaxel, and (iii) enzalutamide after docetaxel. However, we must balance treatment burden against baseline symptoms and the gain from therapy/likeliness of response. The more treatments with a specific therapy a patient can receive, the more likely he has of responding. Monitoring should include scanning when a patient experiences vague symptoms/prostate-specific-antigen rise and avoid switching treatments too late.

Dr. Sweeney mentioned that deciding to use chemotherapy in men with CRPC depends on a number of factors. These include: (i) whether the patient is fit for chemotherapy, (ii) if there is a lack of alternative options with lower treatment burden on a case-by-case basis, and (iii) whether radium-223 with a lower treatment burden is a viable alternative. Docetaxel and cabazitaxel have an adverse-event profile that precludes them from being viable treatment options for all patients, particularly because they are more commonly of older age.

Given the high mutational load associated with CRPC, not everyone is a candidate for androgen-receptor (AR)-targeted therapies. Furthermore, the mutation load may increase over time, as Dr. Sweeney noted that when enzalutamide was given prior to docetaxel, there was an 89% decrease in risk of radiographic progression, but only 60% when given after docetaxel. This implicates the ARv7 mutation and according to Dr. Sweeney, even in the absence of a clinical assay, we can rely on clinical features, namely prior use of abiraterone or enzalutamide (ARv7 is more common in the second line), and an anaplastic variant to ‘assess’ ARv7 status.

Dr. Sweeney concluded that he believes “we will have data showing combinations are more effective than sequential single agents,” especially for high disease burden multiclonal CRPC. He also noted that “we will have biomarkers to guide which agents to combine and newer ones (magnetic resonance imaging/positron emission tomography) will tell us when to switch,” but for now we should rely on symptomatology, current imaging, and PSA. We eagerly await the results of pilot and ongoing trials that are assessing combinatorial therapies.

Presented By: Christopher Sweeney, MD, Dana-Farber Cancer Institute, Boston, MA, USA

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA