Highlights from

ASCO 2019

American Society of Clinical Oncology annual meeting

Chicago, USA 31 May - 4 June 2019

Prostate cancer: Early enzalutamide substantially improves time to progression and overall survival when added to standard mHSPC therapy (testosterone suppression ± docetaxel)

An interim analysis of the international randomised, phase 3 ENZAMET trial found that 80% of men with metastatic hormone-sensitive prostate cancer (mHSPC) who received the non-steroidal anti-androgen (NSAA) medicine enzalutamide along with the standard-of-care treatment were alive after 3 years compared with 72% of men who received other NSAAs along with standard treatment. The study was presented in ASCO’s late-breaking plenary session by Prof. Christopher Sweeney (Dana-Farber Cancer Institute, Boston, USA) for the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group [1].

Enzalutamide is a second-generation androgen antagonist approved for metastatic castration-resistant prostate cancer. Enzalutamide’s anti-androgen mechanism is through binding of the androgen receptor (AR), inhibiting nuclear translocation of AR and subsequent AR binding of DNA [2]. The study presented by Prof. Sweeney found that enzalutamide is a more effective inhibitor of the androgen receptor than bicalutamide, nilutamide, or flutamide, the comparison standard NSAAs used in the trial, but it can lead to different side effects.

Men with mHSPC were randomly assigned between March 2014 and March 2017 to receive an injection of a testosterone-suppressing medicine (such as goserelin, leuprolide, or degarelix) with either a 160-milligram enzalutamide pill daily or one of three standard NSAAs: bicalutamide, nilutamide, or flutamide. Of the 1,125 men enrolled in the trial, 503 men received early doses of docetaxel and 602 did not. Men were followed for a median of 34 months.

After 3 years, 80% of men with mHSPC who received enzalutamide along with testosterone suppression, with or without early docetaxel, were alive compared with 72% of men who received one of the other three NSAAs in the trial. Overall, there was a 33% decrease in the risk of death in men receiving enzalutamide compared to those who took an NSAA.

Researchers further analysed the data to identify the impact of enzalutamide in key groups at the 3-year mark:

• Of 596 men with a higher burden of disease on imaging scans, 71% taking enzalutamide were alive compared with 64% taking another NSAA.

• Of 529 men with a low burden of disease on imaging scans, 90% taking enzalutamide were alive compared with 82% taking another NSAA.

• The increase in survival with enzalutamide was most obvious in men who did not receive docetaxel: among patients who received enzalutamide without docetaxel, 83% were alive compared with 70% taking another NSAA.

• 64% of men were still taking enzalutamide compared with 36% of men taking another NSAA at the time of the first analysis of the data.

Serious adverse events occurred in 42% of men taking enzalutamide compared with 34% of the men taking one of the other NSAAs. Prof. Sweeney noted that a survival benefit is not seen with docetaxel in men with a low volume of disease, but that enzalutamide does improve survival in these men. Enzalutamide is a new option for men with mHSPC and is superior to current standard therapy.

  1. Sweeney C et al. Abstract LBA2. Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial. ASCO 2019, 31 May-4 June, Chicago, USA.

  2. Dhawan M, Ryan CJ. Utility of novel androgen receptor therapies in the real world: A nuanced approach. Urol Oncol. 2016 Aug;34(8):340-7.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.