Perspectives on Cutting-Edge Clinical Trials

Abstract

Johannes Czernin, MD, editor in chief of The Journal of Nuclear Medicine, and J er emie Calais, MD, MSc, his colleague at UCLA, talked with Michael Hofman, MBSS, about success and innovation in clinical trial development. Hofman is a nuclear medicine physician at the PeterMacCallumCancer Centre (Melbourne),Australia’s only public hospital dedicated to cancer treatment, research, and education. He has a coappointment at the University of Melbourne and previously completed a fellowship at Guy’s and St. Thomas’s hospital in London (U.K.). He is the director of the Prostate Cancer Theranostics and Imaging Centre of Excellence at Peter Mac. His research focuses on improving outcomes in prostate cancer, and he is engaged in both preclinical and phases 1–3 research. He has led several landmark clinical trials of prostate-specific membrane antigen (PSMA) imaging and therapy, including the ProPSMA (PSMA PET/CT in patients with high-risk cancer before curativeintent surgery or radiotherapy) study, which has established PSMA PET/CT as a replacement for standard CT and bone scanning, and the TheraP (Lu-PSMA617 theranostic vs. cabazitaxel in progressive metastatic castration-resistant prostate cancer) study. He has authored or coauthoredmore than 200 peer-reviewed articles and is a scientific member of the Australasian Radiopharmaceutical Trials Network (ARTnet) and a board member of the SNMMI Theranostic Center of Excellence. In these roles, he aims to advance the field through clinical trial development and execution. He is an editor for several international journals, including The Journal of Nuclear Medicine. Dr. Czernin: Thank you for participating in today’s leadership discussion. You have had great success in designing, executing, and publishing large-scale clinical trials. The latest example is the TheraP trial (1), published in The Lancet earlier this year. We are going to talk about your path to becoming a world-leading imaging and theranostic trial designer. Dr.Calais:Congratulations on all the great studies you have published. You have become a role model for the younger generation, and your work attracts new trainees to the field. Can you tell us a little bit about your training and how your career in nuclear medicine and theranostics started? Dr. Hofman: Thanks, Johannes and J er emie. It’s a pleasure and honor to share my journey with you. I initially trained in internal medicine, which is the main pathway to nuclear medicine in Australia, along with radiology. In my training, I cycled through nearly all the medical specialties. I had a background in computer science and was always seeking ways to combine my IT skills and medicine. I stumbled on nuclear medicine. When I finished my nuclear medicine training in Melbourne, I did a 12-mo clinical research fellowship at Guy’s and St. Thomas’s in London in 2005 and 2006, exposing me to a high-quality academic environment. When I returned to Melbourne, I worked as an attending physician in a combination of private practice and public hospital environments for 3 years. I really enjoyed it but missed the academic environment. At that time the Peter MacCallumCancerCentre, led byRodney Hicks, MD, was looking for an additional faculty member. It was a pioneering department with good infrastructure and a world-leading neuroendocrine tumor program. It was the only department in Australia performing GaDOTATATEPET imaging. I joined andwas embedded into the neuroendocrine tumor program and saw its remarkable value, on both the imaging and the therapeutic sides. And I really liked the mix of PET scanning, therapy, and research. Dr. Calais: How did you become a “trialist”? Dr.Hofman: I developed a research interest and expertise in lymphoma PET, Ga radiopharmaceuticals, and neuroendocrine tumors, and I had some nice publications in these domains. We succeeded in publishing our data in The Journal of Nuclear Medicine, which was a fantastic outcome for me at the time, but I realized it was not changing global practice. In addition, when I went to oncology conferences, the audiencewas skeptical about the quality of data that we were producing in nuclear medicine. One of my favorite papers that we authored cycled through submission to 4 highimpact oncology journals, who did not even send the paper out for peer review. Responseswere along the lines of “Thank you, Dr. Hofman. This is very nice data, but it’s limited by its single center and retrospective nature. Please, consider doing this prospectively and resubmitting your data.” I reflected on the range of bias inherent in retrospective versus prospective research. I saw my first Tcand Ga-PSMA images at the European Association of Nuclear Medicine meeting in Birmingham in 2011. The extraordinary tumor contrast resonated with me, and I flagged it as my image of the conference and a potential game changer for prostate cancer. Further data in 2012 coming from Germany for imaging and treatment reinforced this. I thought: rather than doing this as an ad hoc imaging test or compassionate access treatment, why not do this as part of well-designed prospective trials? Michael Hofman, MBSS