Daniel J. George, MD

Daniel J. George, MD

Duke University School of Medicine

Durham, North Carolina

Dr. Daniel J. George is a Professor of Medicine and Surgery, Divisions of Medical Oncology and Urology in the Duke University School of Medicine. He also has appointments in the Duke Clinical Research Institute and the Duke Cancer Institute where he is Co-leader for the DCI Center for Prostate and Urologic Cancers. He an internationally recognized clinical researcher and thought leader in GU malignancies, with over 150 peer-reviewed publications. His areas of research include new drug development and biomarkers of GU cancers with an emphasis on health disparities. Dr. George is principal investigator of the Duke site for the Department of Defense (DOD) Prostate Cancer Clinical Trials Consortium since 2006, specializing in Phase I and II studies in prostate cancer. He is also the PI of the MaRCC registry in advanced renal cell carcinoma and Co-PI of the PCF 5000, an international, multi-sponsor supported registry in advanced prostate cancer. Nationally, Dr. George has served on the ASCO scientific committee and the Conquer Cancer Foundation grants review committee, and is chair for 2019-20. He alsoserves on two grant committees for AACR. He is the scientific leader for kidney cancer in the Alliance Cooperative Group since 2011 and serves on the Alliance GU scientific committee, NCI GU Steering Committee and the NCI Renal Task Force. He serves as a senior editor for Clinical Cancer Research and Co-editor in Chief of Clinical Advances in Hematology and Oncology.


Talks by Daniel J. George, MD

Phase 3 VISION Study of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer

Daniel J. George, MD, Professor of Oncologic and Urologic Medicine and Surgery at Duke University, reviews the results of the VISION phase 3 study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. He begins by describing 177Lu-PSMA-617, explaining how it binds to PSMA and causes DNA damage and cell death in cancer. Dr. George then introduces the VISION study, discussing its two arms (standard-of-care, or SOC, and 177Lu-PSMA-617 based treatment vs. SOC alone), as well as its primary endpoints (radiographic progression-free survival, or rPFS, and overall survival). He also highlights the impact of an early dropout rate of 56% in the SOC arm which required enhanced study site education and communication to overcome and resulted in 2 study populations. Dr. George then summarizes the baseline characteristics of the patient populations before detailing the results. He states that 177Lu-PSMA-617 improved rPFS in OS, as shown by the SOC plus 177Lu-PSMA-617-based treatment arm having a higher median survival of 3-5 months. Dr. George then notes that 177Lu-PSMA-617 plus SOC had a 42% partial response rate, a 9.2% complete response rate, and an overall response rate of 50%, whereas SOC alone had a 3% partial response rate and no complete response rate. He states that 177Lu-PSMA-617 with SOC also created a 50% or greater decline in PSA in 46% of patients compared to SOC alone doing the same in only 7.1%. Dr. George discloses that fatigue, bone marrow suppression, dry mouth, nausea and vomiting, renal effects, second primary malignancies, and intracranial hemorrhage are all side effects of this treatment. He concludes that in a heavily pretreated and PSMA-enriched population 177Lu-PSMA-617 demonstrated clinically and statistically significant improvement in OS, rPFS, PSA, and objective responses.

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TheraP Trial and Effectiveness of Lu-PSMA-617

Daniel J. George, MD, Professor of Medicine and Surgery, Divisions of Medical Oncology and Urology at Duke University, comments on the TheraP trial that was presented at the 2021 GU ASCO conference. He reviews the results of the study, compares prior research, and discusses side effects of the treatment. The TheraP trial compared Lu-PSMA-617 against cabazitaxel in mCRPC patients with prior docetaxel chemotherapy. Dr. George contrasts this trial with the VISION study that analyzed patient response to abiraterone and enzalutamide during the chemorefractory setting, but which lacked a comparison to cabazitaxel. He emphasizes that the TheraP trial used two PET scans to identify PSMA-dominant tumors and excluded patients with FDG-positive tumors. This subset of patients was then assigned to either cabazitaxel or Lu-PSMA-617. Results showed increased progression-free survival as well as a decline in PSMA. Dr. George describes some of the side effects of Lu-PSMA-617 and concludes that it may be an optimal option, especially for patients with FDG-negative tumors.

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Relugolix and Concomitant Treatment for Advanced Prostate Cancer

Daniel J. George, MD, Professor of Medicine and Surgery, Divisions of Medical Oncology and Urology in the Duke University School of Medicine, comments on research presented at the 2021 GU ASCO conference about the recent approval of Relugolix and concomitant therapies. He first notes the results of the HERO trial in which Relugolix was shown to be superior to Leuprolide in continuous suppression of testosterone levels in men with advanced prostate cancer. As a follow up to the study, researchers looked at a subset of patients who received concomitant treatment, either radiation therapy to metastatic or primary disease site or drug therapy with Docetaxel or Enzalutamide. Dr. George highlights that patients on Relugolix and additional drug therapy had continued testosterone suppression equal to those on Relugolix alone and lower testosterone levels than patients on Leuprolide. He adds that there were no safety concerns with regard to toxicity. Notably, the HERO trial found a 54% reduction in serious cardiovascular events between Relugolix and Leuprolide. In summary, the study suggests that Relugolix can be safely combined with other therapies and that additional research is needed.

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The HERO Study and the Approval of Relugolix

E. David Crawford, MD, Professor of Urology at UC San Diego and Editor-in-Chief of Grand Rounds in Urology, interviews Neal D. Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, and Daniel J. George, MD, Director of Genitourinary Oncology at Duke Cancer Center, about relugolix, which became the first oral testosterone-suppressive drug approved by the FDA on Friday, December 18, 2020. Drs. Shore and George discuss the results of the international, randomized HERO study, which looked at patients with advanced prostate cancer and found that relugolix, a daily oral GNRH antagonist, had a 97% sustained T-suppression rate as compared to leuprolide’s 88% sustained T-suppression rate. In addition to this high degree of efficacy, they emphasize that patients taken off relugolix saw their testosterone return to higher levels within 90 days than patients taken off leuprolide, which is important for patient quality-of-life. Drs. Shore and George also underline that patients in the relugolix arm of the HERO study saw a more than 50% reduction in risk of major adverse cardiovascular events compared with patients in the leuprolide arm, which suggests that relugolix might be a safer option for prostate cancer patients at high cardiovascular risk. Other topics covered include the benefits of antagonists versus agonists and the possible risks of patient non-compliance.

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