MESSAGE FROM THE CHAIR

Welcome to this edition of UPdate, the newsletter of the Australian & New Zealand Urogenital and Prostate Cancer Trials Group Ltd (ANZUP)!

The chaos and excitement of ASCO, with our plenary presentation and our simultaneous NEJM paper, are now well behind us . Don’t be fooled though into thinking that things have quietened down for ANZUP: it might appear that way, but everything is relative!

1.ENZAMET: the action there is by no means finished . Martin Stockler presented some of the hot-off-thepress quality of life data at ESMO in September . This work showed that there were some early impairments in specific aspects of quality of life for me receiving enzalutamide on the trial, but overall we found improvement in deterioration-free survival (defined as the earliest of death, clinical progression, cessation of study treatment, or clinically important worsening from baseline scores in pertinent quality of life subscales) . The early impairments due to side effects were insufficient to outweigh the benefits in terms of delay in clinical progression or improved survival . This is important: we need to understand the effects on our patients of introducing treatments earlier (and possibly for much longer) in their treatment course . This work gives us confidence that we are having positive impact in areas important to patient well-being and beyond the main trial endpoints of survival or progression . We are here to improve things for our patients and their families: that’s in our mission, and here is level 1 evidence that we are doing it .

There has been widespread uptake of the information out of ENZAMET . People were obviously interested in the main findings, but I think many were surprised that we did not find an overall survival benefit by adding docetaxel to the mix . That’s not to say there isn’t one: we just didn’t detect it at this interim analysis, and there is a benefit in secondary endpoints such as PSA or clinical progression, so the possibility exists that we might see something in the future . However, one important message from ENZAMET did get out and we think this will alter practice: clinicians in places like the USA that have access to multiple agents should not assume that if A is good, and B is good, then A+B = even better . “It seemed like a good idea” is not good enough for our patients when we have evidence of this quality to suggest otherwise .

Hot off the press - this week the US FDA approved the use of enzalutamide for men with metastatic hormonesensitive prostate cancer (mHSPC) . And although this is not yet approved in Australia, it’s a great step forward and another option for men in the US with mHSPC .

There is far more to come for ENZAMET . We plan to report longer term outcomes, especially for that group of patients who did well on both arms and so were not included in the interim analysis . We want to look further at the effects of the combination with docetaxel . We are planning detailed translational studies, and health economic studies, and no doubt many more riches will fall into our hands from this work .

2.Other current studies: Look around you at the ANZUP portfolio: it is booming! Since the last UPdate we have completed recruitment to UNISoN, TheraP and Pain Free TrusB . Three very important trials that may well change practice in the future . I won’t go into them all (you will read more inside this newsletter), but here’s a taste of what else is on offer:

• UNICAB: an opportunity to use cabozantinib for non-clear-cell renal cell carcinoma patients who have received prior immunotherapy (mostly patients previously on UNISoN) – now open .