Precision Medicine Clinical Trials

Lale Kostakoglu, MD, MPH, a professor of Radiology and Chief of Nuclear Medicine and Molecular Imaging in the University of Virginia Health System (Charlottesville, VA), talked with Peter J. O’Dwyer, MD, a professor of Medicine at the University of Pennsylvania (Philadelphia) and a medical oncologist with expertise in gastrointestinal (GI) and pancreatic cancers. Dr. O’Dwyer has been the Group Co-Chair of the ECOG-ACRIN Cancer Research Group since May 2017. ECOG-ACRIN is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. The network includes more than 1,300 academic and community-based cancer centers and hospitals in the United States and around the world, with approximately 15,000 oncology professionals involved in sponsored research. Within ECOG-ACRIN, Dr. O’Dwyer co-chairs the landmark National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (MATCH) precision medicine cancer trial. He is the CEO and chair of the Board of Managers of PrECOG, LLC, and president of the ECOG Research and Education Foundation. Dr. O’Dwyer received his medical degree from the University of Dublin, Trinity College (Ireland), and completed his residency at the Hammersmith Hospital (London, U.K.). After a fellowship at the Baltimore Cancer Research Center (MD), he became a senior investigator in the Division of Cancer Treatment at NCI (Bethesda, MD). He previously led the Developmental Therapeutics Programs at Fox Chase Cancer Center (Philadelphia, PA) and the University of Pennsylvania. He has authored more than 350 scientific articles and participates in numerous national and international organizations. Dr. Kostakoglu: Let’s start with your inspiring trans-Atlantic experience. Would you like to tell us about your background and the pivotal decisions that shaped your career path? Dr. O’Dwyer: That’s an interesting question. Actually, my career path has been formed in the United States. I have links with Europe just because many of my colleagues through the years have gone from junior to more mature positions there, and a lot of research is based on personal links. We’re fortunate within ECOG-ACRIN to have a strong presence in Europe, South America, Asia, and Canada to establish new member relationships. Particularly in Asia, where South Korea is the most important country for us to focus on right now because we have shared studies there. It’s been difficult to go beyond that because of various regulatory issues, particularly in South America. To generate scientific ideas and design new trials, we often collaborate with global research consortia, such as the International Rare Cancers Initiative and others. I think these international interactions really help us focus on the global impact of our studies and assist us in carrying out ECOG-ACRIN’s strong commitment to advancing standards of care in broad populations of cancer patients and those at risk. We seek patient diversity in all clinical trials, including AfricanAmerican patients, patients with Hispanic ethnicity, and Asian groups. For example, our current Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is highly diverse. I think that precision medicine, where we tailor treatment to the individual, is helping us increase awareness of how important it is to include diverse patient populations in our trials to ensure that the results apply to all. Dr. Kostakoglu: Thank you so much for that background. Can we talk about your leadership role more specifically now? You’re wearing at least 2 hats: 1 as an active researcher in the GI and developmental therapeutics programs at the University of Pennsylvania and the other as the national co-chair of the ECOG-ACRIN group. If we start from developmental therapeutics, could you tell us what this focus fosters and how it integrates translational research with clinical program resources? Dr. O’Dwyer: Although I continue to see patients at the Abramson Cancer Center at the University of Pennsylvania, I have relinquished any UPenn leadership roles to focus more on ECOGACRIN. But, certainly, developmental therapeutics has informed my approach to clinical research in GI cancers and more broadly. Having had responsibility for an R01-funded research lab for about 20 years, this type of research is my background. Developmental therapeutics programs are the main idea generators for clinical research; our role is to link academic medical centers to a broader community to allow translational research efforts to have maximum impact. Unfortunately, resources from the government are decreasing. Now, more than ever, institutions need to develop partnerships to be able to conduct these studies. We’re constantly talking with the senior leadership of the NCI about ways to increase the impact of translational research. Dr. Kostakoglu: Shifting the topic to novel therapeutics, we know that owing to the highly adaptive nature of cancers, there is definitely a need for new therapeutic strategies. But what are the principal mechanisms for these novel targeted therapeutics in circumventing the barriers of conventional treatments? Peter J. O’Dwyer, MD