ANZUP is an organisation that promotes research and clinical trials for cancers such as prostate cancer. The 2018 ANZUP meeting brought together national and international experts to discuss the latest innovations and issues in research and clinical practice. This week's research blog describes some of the meeting highlights for prostate cancer.
ANZUP is the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. ANZUP's mission is to conduct clinical trial research to improve treatment of bladder, kidney, testicular and prostate cancers. The organisation is currently celebrating its 10-year anniversary.
PCFA staff recently attended the 7th ANZUP Annual Scientific Meeting in Sydney. The theme of ANZUP 2018 was Putting people first. This set the tone for many of the talks, with experts often asking themselves whether they really were putting people first in their clinical practice, trials and research. ANZUP 2018 featured a symposium for PCFA's Prostate Cancer Specialist Nurses, a clinical trial concept development session, overviews of current and planned ANZUP trials and a community engagement forum.
As in previous meetings, ANZUP 2018 featured a report from their consumer advisory panel. This panel provides a mechanism for advice to be offered on specific studies, general research directions, and priorities, from the perspective of consumers (patients, survivors, families and others affected by cancer). The consumer advisory panel also provides communication from ANZUP back to the community in order to promote research and engage community support.
The ANZUP 2018 meeting also featured a Translational Research Symposium. Research was presented that aims to transform basic (laboratory) scientific discoveries into interventions that improve the lives of people affected by prostate cancer. During this meeting, presentations by the leaders of two Movember Revolutionary Team Awards gave updates on their projects. Administered by PCFA, these large Movember-funded grants bring together some of Australia's most important researchers to take a collaborative approach in researching the clinical management of prostate cancer. The aim of the Movember Revolutionary Team Awards is to fund teams to make major advances in prostate cancer research. A/Prof Lisa Butler presented the latest results from her research team, based at the South Australian Health and Medical Research Institute/University of Adelaide. Prof Colleen Nelson gave an update on her team's research, conducted at the Translational Research Institute in Brisbane.
A/Prof Lisa Butler: New insights into prostate tumour heterogeneity from studying the "lipidome".
A/Prof Butler spoke about her research project that uses analysis of fat metabolism to understand the different types of prostate cancer. A/Prof Butler's team are able to study the Lipidome of tumour cells. The Lipidome is essentially a profile of all fat and oil molecules in cells - how many and what type of molecules. The lipid profile is a kind of "molecular signature" that tells us about the nature of a cell. The way that fat and oil molecules are broken down and used is different in prostate cancer cells compared to normal body cells. A/Prof Butler's research asks whether the lipid profile of a prostate tumour carries information that can predict how the tumour will behave in the future.
A/Prof Butler's team have shown that prostate tumours have more molecules called mono-unsaturated phospholipids than normal tissue. They also have longer fatty acid molecules. These changes are likely to enhance the cancer cells' ability to move, possibly aiding tumour metastasis to distant sites. She has also shown that the lipid profile is associated with the Gleason score and disease aggressiveness. In laboratory-grown tumour cells, inhibition of testosterone activity using the drug Enzalutamide (Xtandi) leads to changes in the lipid profile. Targeting specific lipid profiles with drugs in laboratory experiments could reduce the growth of prostate tumours.
This project has shown that prostate tumours carry their own lipid profile (list of all types of fat and oil molecules present). Measuring this profile tells us about the kind of tumour and how it might respond to treatment. Drugs might be capable of targeting tumours based on differences in lipid profiles that are different to normal cells.
Prof Colleen Nelson: Drugging pathways activated by androgen-targeted therapies in prostate cancer.
Prof Colleen Nelson's project aims to improve therapies that inhibit testosterone. Testosterone drives the growth of prostate cancer cells. So many of the current drugs aim to reduce the effect of testosterone and similar male hormones. Unfortunately prostate cancers can adapt to these therapies, finding ways around the effects of the drug, to keep growing. Prof Nelson's team aims to find drugs that target the methods that prostate cancer uses to escape anti-hormone therapies.
Therapies that target male hormones often lead to symptoms and features of metabolic syndrome (obesity, high blood pressure, high blood sugar levels etc). This leads to increased levels of insulin and a hormone called leptin in the blood. Men who have these features are more likely to see their cancer progress. Prof Nelson predicts that insulin may be able to "take-over", by driving cancer cell growth when testosterone is inhibited. Her group are testing ways to prevent insulin from doing this. They have successfully used mouse experiments to show that combining anti-hormone treatments with anti-insulin drugs can reduce tumour progression. They are currently testing whether the diabetes drug Metformin will help delay the failure of anti-hormone drugs. Metformin is a commonly-used diabetic medication that lowers insulin and helps people to lose weight.
Overview of ANZUP prostate cancer clinical trials
The progress of four prostate cancer clinical trials was reported at ANZUP:
- ENZAMET - an international phase 3 randomised controlled trial
This trial tests the use of Enzalutamide (Xtandi) as a first-line androgen deprivation therapy (ADT) for men with metastatic prostate cancer. In this trial, men with metastatic prostate cancer starting ADT also took Enzalutamide. These men are being compared to a control group taking standard ADT only. The ENZAMET trial asks whether early Enzalutamide increases survival. It also asks whether the treatment is safe, delays disease progression, is cost effective and improves quality-of-life.
This trial is on-going, as it will be many years before survival outcomes are known. But the good news is that the ENZAMET trial has successfully recruited for all places. 1,125 men have joined the trial, from 83 different sites. 684 of these men were Australians, 195 were recruited in Ireland and UK, 204 in Canada and 42 in the US. The ENZAMET trial is now in a follow-up phase. The first interim analysis is due next year, giving an indication as to whether the early use of Enzalutamide makes a difference for men with metastatic prostate cancer. In presenting this update, Prof Chris Sweeney was optimistic that the trial was going very well and predicts a good result.
- ENZARAD - an international phase 3 randomised controlled trial
The ENZARAD trial tests the use of Enzalutamide (Xtandi) as an early therapy for men with high-risk localised prostate cancer. Men taking ADT after radiotherapy are being treated for 2 years with Enzalutamide. They are compared to men taking ADT after radiotherapy without the Enzalutamide. The radiotherapy for these men was external body radiotherapy (EBRT) with a brachytherapy boost. All the men received radiotherapy directed at their prostate and at lymph nodes if necessary.
The ENZARAD trial has successfully recruited all places. Recruitment of 802 men closed recently on 30th June 2018. 503 Australian men joined the trial, together with 179 from Ireland, 106 from the USA and 14 from Europe. These men are now being followed-up by the trial to compare outcomes. The major question asked by this trial is whether using early Enzalutamide will increase survival times for these men. Other measures will include PSA levels, progression to metastatic disease, quality-of-life and costs. These measures will be made 5 years after starting the therapy. An interim analysis showed the trial was going well. In presenting this update, Prof Scott Williams explained how blood and tissue samples provided by patients have been carefully stored to help future studies
- TheraP - an Australian phase 2 randomised controlled trial
TheraP is a new trial that opened in January 2018. The aim is to test a new treatment called Lu177-PSMA for men with metastatic castration-resistant prostate cancer. Half the men in this trial will received the new Lu177-PSMA treatment. They will be compared to men receiving the current standard treatment of Cabazitaxel (Jevtana) chemotherapy.
The primary aim of this trial is to determine the safety and activity of the Lu177-PSMA treatment. The trial will also measure PSA levels, pain levels, cancer progression, survival time and quality-of-life. 28 patients have been recruited so far, out of a planned total of 200. It's anticipated that this trial will continue recruiting until December 2019. There are 11 hospitals participating in this trial in Australia, with 7 more site that we hope will open soon.
TheraP is an ANZUP trial funded by PCFA and Movember. More information about this trial can be found on our website.
- Pain-free TRUS B - An Australian/New Zealand phase 3 randomised controlled trial
The aim of the TRUS-B trial is to test whether the painkiller methoxyflurane (Penthrox), plus local anaesthetic, reduces pain for men having their first prostate TRUS biopsy. Men having TRUS biopsy (transrectal ultrasound-guided biopsy) with methoxyflurane and local anaesthetic are being compared to a control group who have local anaesthetic alone.
The primary readout for this trial is the patient's rating of pain levels. Patients are asked 15 minutes after the biopsy how much pain they felt. The trial is also assessing other factors such as the willingness to undergo a biopsy in the future and the safety of the procedure. Men are being recruited through 8 different sites in Australia and New Zealand. So far, 235 of a planned total of 420 men have joined the trial. The co-ordinators hope that the trial will finish recruitment by the middle of 2019. More information about this trial can be found at this website.
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