Daniel George

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in Surgery

Surgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1992

Duke University

Medical Resident, Medicine

Johns Hopkins University

Fellow in Medical Oncology, Medicine

Johns Hopkins University

Grants:

Plasma Angiome and Serum Androgens as Predictors of Overall Survival in Metastatic Prostate Cancer

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Collaborator
Start Date
End Date

Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Collaborating Investigator
Start Date
End Date

Disparities in the Use of Oral Anticancer Agents in Kidney Cancer

Administered By
Population Health Sciences
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing CB-839 in Combination with Cabozantinib (CB-Cabo) vs. Placebo with Cabozantinib (Pbo-Cabo) in Patients with Advanced or Metastatic Renal Cell Carcinoma (RCC)

Administered By
Duke Cancer Institute
Awarded By
Calithera Biosciences, Inc.
Role
Principal Investigator
Start Date
End Date

A Phase II open-label, Multicenter study of Apalutamide, Abiraterone Acetate and Prednisone in African American and Caucasian men with metastatic castrate-resistant prostate cancer

Administered By
Duke Cancer Institute
Awarded By
Janssen Pharmaceutica, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.
Authors
George, DJ; Halabi, S; Heath, EI; Sartor, AO; Sonpavde, GP; Das, D; Bitting, RL; Berry, W; Healy, P; Anand, M; Winters, C; Riggan, C; Kephart, J; Wilder, R; Shobe, K; Rasmussen, J; Milowsky, MI; Fleming, MT; Bearden, J; Goodman, M; Zhang, T; Harrison, MR; McNamara, M; Zhang, D; LaCroix, BL; Kittles, RA; Patierno, BM; Sibley, AB; Patierno, SR; Owzar, K; Hyslop, T; Freedman, JA; Armstrong, AJ
MLA Citation
URI
https://scholars.duke.edu/individual/pub1481831
PMID
33951180
Source
pubmed
Published In
Cancer
Published Date
DOI
10.1002/cncr.33589

Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

PURPOSE: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). PATIENTS AND METHODS: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. RESULTS: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). CONCLUSION: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
Authors
Scher, HI; Armstrong, AJ; Schonhoft, JD; Gill, A; Zhao, JL; Barnett, E; Carbone, E; Lu, J; Antonarakis, ES; Luo, J; Tagawa, S; Dos Anjos, CH; Yang, Q; George, D; Szmulewitz, R; Danila, DC; Wenstrup, R; Gonen, M; Halabi, S
MLA Citation
Scher, H. I., et al. “Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.Eur J Cancer, vol. 150, Apr. 2021, pp. 83–94. Pubmed, doi:10.1016/j.ejca.2021.02.042.
URI
https://scholars.duke.edu/individual/pub1480561
PMID
33894633
Source
pubmed
Published In
Eur J Cancer
Volume
150
Published Date
Start Page
83
End Page
94
DOI
10.1016/j.ejca.2021.02.042

Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry.

Prostate cancer disproportionately affects racial and ethnic minority populations. Reasons for disparate outcomes among minority patients are multifaceted and complex, involving factors at the patient, provider, and system levels. Although advancements in our understanding of disease biology have led to novel therapeutics for men with advanced prostate cancer, including the introduction of biomarker-driven therapeutics, pivotal translational studies and clinical trials are underrepresented by minority populations. Despite attempts to bridge the disparities gap, there remains an unmet need to expand minority engagement and participation in clinical trials to better define the impact of therapy on efficacy outcomes, quality of life, and role of biomarkers in diverse patient populations. The IRONMAN registry (ClinicalTrials.gov identifier: NCT03151629), a global, prospective, population-based study, was borne from this unmet medical need to address persistent gaps in our knowledge of advanced prostate cancer. Through integrated collection of clinical outcomes, patient-reported outcomes, epidemiologic data, and biospecimens, IRONMAN has the goal of expanding our understanding of how and why prostate cancer outcomes differ by race and ethnicity. To this end, the Diversity Working Group of the IRONMAN registry has developed informed strategies for site selection, recruitment, engagement and retention, and trial design and eligibility criteria to ensure broad inclusion and needs awareness of minority participants. In concert with systematic strategies to tackle the complex levels of disparate care, our ultimate goal is to expand minority engagement in clinical research and bridge the disparities gap in prostate cancer care.
Authors
McKay, RR; Gold, T; Zarif, JC; Chowdhury-Paulino, IM; Friedant, A; Gerke, T; Grant, M; Hawthorne, K; Heath, E; Huang, FW; Jackson, MD; Mahal, B; Ogbeide, O; Paich, K; Ragin, C; Rencsok, EM; Simmons, S; Yates, C; Vinson, J; Kantoff, PW; George, DJ; Mucci, LA
MLA Citation
McKay, Rana R., et al. “Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry.Jco Glob Oncol, vol. 7, Apr. 2021, pp. 495–505. Pubmed, doi:10.1200/GO.20.00571.
URI
https://scholars.duke.edu/individual/pub1478276
PMID
33835826
Source
pubmed
Published In
Jco Glob Oncol
Volume
7
Published Date
Start Page
495
End Page
505
DOI
10.1200/GO.20.00571

Immunotherapy and targeted-therapy combinations mark a new era of kidney cancer treatment.

Authors
MLA Citation
Zhang, Tian, and Daniel J. George. “Immunotherapy and targeted-therapy combinations mark a new era of kidney cancer treatment.Nat Med, vol. 27, no. 4, Apr. 2021, pp. 586–88. Pubmed, doi:10.1038/s41591-021-01320-x.
URI
https://scholars.duke.edu/individual/pub1478277
PMID
33820997
Source
pubmed
Published In
Nat Med
Volume
27
Published Date
Start Page
586
End Page
588
DOI
10.1038/s41591-021-01320-x

A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial.

BACKGROUND: MET (also known as hepatocyte growth factor receptor) signalling is a key driver of papillary renal cell carcinoma (PRCC). Given that no optimal therapy for metastatic PRCC exists, we aimed to compare an existing standard of care, sunitinib, with the MET kinase inhibitors cabozantinib, crizotinib, and savolitinib for treatment of patients with PRCC. METHODS: We did a randomised, open-label, phase 2 trial done in 65 centres in the USA and Canada. Eligible patients were aged 18 years or older with metastatic PRCC who had received up to one previous therapy (excluding vascular endothelial growth factor-directed and MET-directed agents). Patients were randomly assigned to receive sunitinib, cabozantinib, crizotinib, or savolitinib, with stratification by receipt of previous therapy and PRCC subtype. All drug doses were administered orally: sunitinib 50 mg, 4 weeks on and 2 weeks off (dose reductions to 37·5 mg and 25 mg allowed); cabozantinib 60 mg daily (reductions to 40 mg and 20 mg allowed); crizotinib 250 mg twice daily (reductions to 200 mg twice daily and 250 mg once daily allowed); and savolitinib 600 mg daily (reductions to 400 mg and 200 mg allowed). Progression-free survival (PFS) was the primary endpoint. Analyses were done in an intention-to-treat population, with patients who did not receive protocol therapy excluded from safety analyses. This trial is registered with ClinicalTrials.gov, NCT02761057. FINDINGS: Between April 5, 2016, and Dec 15, 2019, 152 patients were randomly assigned to one of four study groups. Five patients were identified as ineligible post-randomisation and were excluded from these analyses, resulting in 147 eligible patients. Assignment to the savolitinib (29 patients) and crizotinib (28 patients) groups was halted after a prespecified futility analysis; planned accrual was completed for both sunitinib (46 patients) and cabozantinib (44 patients) groups. PFS was longer in patients in the cabozantinib group (median 9·0 months, 95% CI 6-12) than in the sunitinib group (5·6 months, 3-7; hazard ratio for progression or death 0·60, 0·37-0·97, one-sided p=0·019). Response rate for cabozantinib was 23% versus 4% for sunitinib (two-sided p=0·010). Savolitinib and crizotinib did not improve PFS compared with sunitinib. Grade 3 or 4 adverse events occurred in 31 (69%) of 45 patients receiving sunitinib, 32 (74%) of 43 receiving cabozantinib, ten (37%) of 27 receiving crizotinib, and 11 (39%) of 28 receiving savolitinib; one grade 5 thromboembolic event was recorded in the cabozantinib group. INTERPRETATION: Cabozantinib treatment resulted in significantly longer PFS compared with sunitinib in patients with metastatic PRCC. FUNDING: National Institutes of Health and National Cancer Institute.
Authors
Pal, SK; Tangen, C; Thompson, IM; Balzer-Haas, N; George, DJ; Heng, DYC; Shuch, B; Stein, M; Tretiakova, M; Humphrey, P; Adeniran, A; Narayan, V; Bjarnason, GA; Vaishampayan, U; Alva, A; Zhang, T; Cole, S; Plets, M; Wright, J; Lara, PN
MLA Citation
Pal, Sumanta K., et al. “A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial.Lancet, vol. 397, no. 10275, Feb. 2021, pp. 695–703. Pubmed, doi:10.1016/S0140-6736(21)00152-5.
URI
https://scholars.duke.edu/individual/pub1474699
PMID
33592176
Source
pubmed
Published In
Lancet
Volume
397
Published Date
Start Page
695
End Page
703
DOI
10.1016/S0140-6736(21)00152-5