EAU 2018: Castration Resistant Prostate Cancer

Copenhagen, Denmark (UroToday.com)  Dr. Evans gave an overview of the hottest and latest news in the medical treatment of castrate resistant prostate cancer (CRPC).  In metastatic CPRC (MCRPC), plasma circulating tumor DNA (ctDNA) has emerged as a tool to sample the tumor genome.  Up until recently, no systematic comparisons of matched liquid and solid biopsies were performed to enable ctDNA profiling to replace direct tissue sampling. After this comparison had recently been done, ctDNA sequencing revealed robust changes not present in paired solid biopsy, including clinically relevant alterations in the AR, WNT, and PI3K pathways. Therefore, in most patients, a ctDNA assay is sufficient to identify all driver DNA alterations present in matched metastatic tissue. This supports development of DNA biomarkers to guide MCRPC patients’ management based on ctDNA alone.

According to a recently published study, docetaxel re-challenge following progression to MCRPC after upfront ADT +docetaxel for metastatic hormone sensitive prostate cancer (MHSPC) was beneficial only in a limited number of patients. The available data on abiraterone and enzalutamide support maintained efficacy in this setting. [1] Another recently published study assessed the effect the addition of enzalutamide had in MCRPC patients who progressed after 24 weeks with abiraterone. [2] The primary endpoint was radiographic progression free survival (RPFS) and secondary endpoints were overall survival (OS), PSA response, and time to PSA progression. The results showed that OS was not reached with a median RPFS of 8.1 months. In conclusion, enzalutamide showed antitumor activity in some patients with MCRPC who had previously progressed following 24 weeks of abiraterone treatment.

FIRSTANA, was a study assessing whether Cabazitaxel in different dosages was superior to docetaxel in terms of OS in MCRPC patients who were chemotherapy naïve.[3] The study did not demonstrate superiority of OS in cabazitaxel vs. docetaxel. Tumor response was numerically higher with cabazitaxel vs. docetaxel. The drugs were demonstrated to have different toxicity profiles, but overall less toxicity with cabazitaxel.

PROSPER was a phase 3 randomized, double blind, placebo controlled study of enzalutamide vs. placebo in men with non-metastatic CRPC patients. The study showed a clear advantage to enzalutamide in metastasis free survival (MFS) with 71% reduction in the relative risk of developing metastasis, PSA progression, time to first use of new antineoplastic therapy, with immature results on OS, but with a trend favoring enzalutamide on first interim analysis.

The SPARTAN study [4] compared apalutamide (a new androgen receptor pathway inhibitor) with ADT to placebo with ADT in patients with M0 CRPC in a phase 3 randomized multicenter international trial. The primary endpoint was MFS. This study demonstrated that Apalutamide conferred a 72% survival benefit for patients treated with apalutamide. Time to metastasis was reduced by 73% and progression free survival was improved by 71%.

This is an exciting time with new drug developments, changing the landscape of MCRPC treatment, and hopefully improving the outcomes of these patients.

Presented by: Christopher Evans, UC DAVIS, California, USA

[1] Lavaud et al. Eur. Urol 2017
[2] de Bono et al. Eur Urol 2017
[3] Oudard et al. JCO 2017
[4] Smith et al. N Engl J Med 2018

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