ANZUP at ASCO 2025 – ENZAMET
ENZAMET
Background
Prostate cancer remains the most commonly diagnosed cancer in Australia and New Zealand with over 30,000 people expected to be diagnosed every year. Thanks to world class research, prostate cancer can be treated effectively for the majority of the people affected¹,². Nevertheless, over 4,000 people every year will die due to an advanced or hard-to-treat form of prostate cancer and many more people will have life-long treatment related side-effects including morbidity associated with long-term hormonal suppression, sexual dysfunction and mental health issues³.
Metastatic castration-resistant prostate cancer (mCRPC) is a type of advanced prostate cancer that has spread to other parts of the body and no longer responds to standard hormone therapy, which is meant to lower testosterone. Even though testosterone levels are low, the cancer keeps growing. While it can’t be cured, there are several treatment options that can help slow the cancer down and manage symptoms.
About the trial
Enzalutamide is a new hormone treatment taken as tablets. Previous trials have proven that enzalutamide improves survival and quality of life in people with prostate cancer that has stopped responding to standard hormone treatments and chemotherapy.
This large, international randomised trial was undertaken to determine if treatment with enzalutamide can improve survival and quality of life in people starting hormone treatment for newly diagnosed prostate cancer that has spread beyond the prostate. The trial was led from Australia by ANZUP in collaboration with the NHMRC Clinical Trials Centre. It involved 1,125 people from Australia, New Zealand, Canada, the US, Ireland, and the UK.
In 2020 the ENZAMET trial won all three of the Australian Clinical Trials Alliance (ACTA) Awards. The ENZAMET trial was awarded the 2020 ACTA Trial of the Year Award, the ACTA STInG Award for Excellence in Trial Statistics and the Consumer Involvement Award.
This landmark Australian led clinical trial, ENZAMET, has now shown that hormone therapy with a drug called enzalutamide can improve the survival of some people with advanced, hormone-sensitive prostate cancer. Findings from the ENZAMET trial, led by ANZUP, have shown that people with this sort of cancer who receive enzalutamide with standard treatment have a 33% improvement in survival compared to people receiving standard treatment alone and a 60% improvement in the time it takes to detect the cancer growing again. These results were much better than it was thought they might be when the trial began.
The ANZUP investigator initiated studies were financially supported by Astellas, who also provided enzalutamide.
Poster presentation at the ASCO 2025
At ASCO 2025, three posters on the ENZAMET study were presented.
Poster presented by Dr Alison Zhang. ANZUP’s practice changing ENZAMET trial showed that people diagnosed with metastatic hormone sensitive prostate cancer on testosterone suppression therapy who received the androgen receptor pathway inhibitor enzalutamide, had a longer overall survival compared to those receiving non-steroidal anti-androgen (NSAA) therapy. On the weekend, Dr Zhang presented the latest findings from this trial with a median follow-up of at least 8 years to understand the long-term efficacy and safety of enzalutamide. The results showed participants lived longer on enzalutamide with median overall survival 8.0 years compared to those on NSAA’s who had a median overall survival of 5.8 years. Falls and fractures were higher for participants on enzalutamide, but cardiac and cerebrovascular events had a similar frequency. These results show that enzalutamide treatment results in significant survival benefit for those diagnosed with metastatic hormone sensitive prostate cancer, but the side effects of treatment impacting bone health need consideration and effective management.
Prognostic value of PSMA-PET against CHAARTED criteria in an ENZAMET sub-cohort
Poster presented by Prof Louise Emmett. CHAARTED criteria on conventional imaging (CT and bone scan) is an important prognostic biomarker in metastatic hormone sensitive prostate cancer (mHSPC) that is used to guide treatment intensification; however, clinicians are increasingly using PSMA PET/CT scans in lieu of conventional imaging for staging of prostate cancer. PSMA PET/CT criteria for poor prognostic mHSPC are poorly defined. In a sub-study of ENZAMET, 100 participants (51 enzalutamide, 49 control NSAA) who had PSMA-PET were used to identify features on these scans that correlate to progression free and overall survival. The results showed that total tumour volume on PSMA-PET (PSMA-TTV) is associated with progression free survival in mHSPC and could be potentially used as a prognostic tool.
Poster presentation by Prof Lisa Horvath (pictured with fellow author Prof Anthony Joshua). In another sub-study of the ENZAMET trial, blood based immune and metabolic biomarkers were assessed for their prognostic and predictive ability. At ASCO, Professor Horvath presented the results that showed that circulating IL8, IGFBP1 and the IGF/IGFBP1 ratio was prognostic for overall survival and several pro-inflammatory, anti-tumour and macrophage-associated biomarkers were associated with poorer clinical outcomes in mHSPC. None of the markers were predictive of response to enzalutamide. This study yielded important insights into the development of immune and metabolic prognostic and predictive biomarkers for prostate cancer.
References:
- Cancer Data in Australia, Australian Institute of Health and Welfare (AIHW) 2024
- New Zealand Cancer Registry (NZCR), Health New Zealand-Te Whatu Ora
- National Cancer Control Indicators; relative survival for prostate cancer by stage, 2011