ENZAMET – NEJM, QoL Translational update

Doctors commonly start men newly diagnosed with metastatic prostate cancer on androgen deprivation therapy (otherwise known as ADT), along with a standard anti-androgen tablet (such as Cosudex or Anandron). These drugs work in prostate cancer by shutting off the supply of testosterone, which is the fuel that drives prostate cancer growth. While this standard treatment is very effective, doctors and researchers are constantly striving for ways to improve treatment and increase patient survival from metastatic prostate cancer. The striking results from the ENZAMET clinical trial, presented at the Plenary Session of the 2019 American Society of Clinical Oncology (ASCO) meeting, and published in the New England Journal of Medicine, have achieved just that.

ENZAMET is a large Phase 3 study that shows that giving enzalutamide to men just starting ADT reduced the risk of death at 3-years by a third, relative to giving ADT with the standard anti-androgen drug. Enzalutamide also significantly increased the time until the cancer showed signs of growing, either by symptoms, scans, or rising PSA. Before these findings, enzalutamide was given only to men with metastatic prostate cancer after ADT stopped working. This study now suggests that enzalutamide should be considered much earlier in the course of the disease, around the time of starting ADT when patients are diagnosed with metastatic cancer.

The ENZAMET trial began in 2014 and recruited 1125 patients from 83 medical centres around the world. Men with metastatic prostate cancer starting first-line ADT were enrolled in the study. The average age of the men in the study was 69 years; 11% of men had metastatic disease outside of the bones and lymph nodes. The study is led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.

The positive findings from the ENZAMET trial mean that men with metastatic prostate cancer may have another treatment option.

ENZAMET – Health Related Quality of Life (HRQoL)

Health-related quality of life (HRQoL) in a randomised phase 3 trial of enzalutamide with standard first line therapy for metastatic, hormone-sensitive prostate cancer (mHSPC).

In the ANZUP-led ENZAMET trial, using enzalutamide along with androgen deprivation therapy (ADT) in men with metastatic prostate cancer who were “hormonenaïve” (men just starting ADT), reduced the risk of death, and significantly increase the time until cancer showed signs of growing.

ANZUP researchers know health-related quality of life is very important to men and their families. So in the ENZAMET trial health-related quality of life of participants was measured. ANZUP evaluated aspects of health-related quality of life such as comfort, happiness, and well-being in men who received enzalutamide, and compared their experience with men receiving standard anti-androgen drug.

To study the health-related quality of life in ENZAMET participants, 3 widely-used questionnaires assessed the impact of treatment on several aspects such as physical comfort, mood, appetite, sleep, and sexual function. Men rated their own experience on these questionnaires covering these comprehensive domains.

Pleasingly, the results of the quality of life evaluation revealed that men who received enzalutamide reported their general health was steady and their overall quality of life stable. The use of enzalutamide delayed the onset of unpleasant symptoms. Although enzalutamide treatment negatively affected some aspects of health early on, this did not outweigh the subsequent quality of life benefits in the men’s cancer journey.

Translational work

The ENZAMET trial is proving to be a gold mine for translational research, with planned studies in genomics, cytokines and lipidomics planned for 2021. ANZUP has an engaged world class team of translational researchers who meet regularly to consider the most important cutting-edge questions in order to improve treatment and outcomes for our patients. If you wish to support ANZUP’s Translational Research Program please go to https://anzup.org.au/what-is-gu-cancer/spotlight-on-translational-research/. Other completed trials such as TheraP are also a great reservoir of potential translational sub-studies, and any interested investigators are encouraged to contact the relevant study principal investigator to discuss.