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:

Characterizing the Feasibility and Performance of Real-World Tumor Progression End Points and Their Association With Overall Survival in a Large Advanced Non-Small-Cell Lung Cancer Data Set.

PURPOSE: Large, generalizable real-world data can enhance traditional clinical trial results. The current study evaluates reliability, clinical relevance, and large-scale feasibility for a previously documented method with which to characterize cancer progression outcomes in advanced non-small-cell lung cancer from electronic health record (EHR) data. METHODS: Patients who were diagnosed with advanced non-small-cell lung cancer between January 1, 2011, and February 28, 2018, with two or more EHR-documented visits and one or more systemic therapy line initiated were identified in Flatiron Health's longitudinal EHR-derived database. After institutional review board approval, we retrospectively characterized real-world progression (rwP) dates, with a random duplicate sample to ascertain interabstractor agreement. We calculated real-world progression-free survival, real-world time to progression, real-world time to next treatment, and overall survival (OS) using the Kaplan-Meier method (index date was the date of first-line therapy initiation), and correlations between OS and other end points were assessed at the patient level (Spearman's ρ). RESULTS: Of 30,276 eligible patients,16,606 (55%) had one or more rwP event. Of these patients, 11,366 (68%) had subsequent death, treatment discontinuation, or new treatment initiation. Correlation of real-world progression-free survival with OS was moderate to high (Spearman's ρ, 0.76; 95% CI, 0.75 to 0.77; evaluable patients, n = 20,020), and for real-world time to progression correlation with OS was lower (Spearman's ρ, 0.69; 95% CI, 0.68 to 0.70; evaluable patients, n = 11,902). Interabstractor agreement on rwP occurrence was 0.94 (duplicate sample, n = 1,065) and on rwP date 0.85 (95% CI, 0.81 to 0.89; evaluable patients n = 358 [patients with two independent event captures within 30 days]). Median rwP abstraction time from individual EHRs was 18.0 minutes (interquartile range, 9.7 to 34.4 minutes). CONCLUSION: We demonstrated that rwP-based end points correlate with OS, and that rwP curation from a large, contemporary EHR data set can be reliable, clinically relevant, and feasible on a large scale.
Authors
Griffith, SD; Miksad, RA; Calkins, G; You, P; Lipitz, NG; Bourla, AB; Williams, E; George, DJ; Schrag, D; Khozin, S; Capra, WB; Taylor, MD; Abernethy, AP
MLA Citation
URI
https://scholars.duke.edu/individual/pub1404481
PMID
31403818
Source
pubmed
Published In
Jco Clinical Cancer Informatics
Volume
3
Published Date
Start Page
1
End Page
13
DOI
10.1200/CCI.19.00013

Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients

© 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.
Authors
Zhang, T; Pabla, S; Lenzo, FL; Conroy, JM; Nesline, MK; Glenn, ST; Papanicolau-Sengos, A; Burgher, B; Giamo, V; Andreas, J; Wang, Y; Bshara, W; Madden, KG; Shirai, K; Dragnev, K; Tafe, LJ; Gupta, R; Zhu, J; Labriola, M; McCall, S; George, DJ; Ghatalia, P; Dayyani, F; Edwards, R; Park, MS; Singh, R; Jacob, R; George, S; Xu, B; Zibelman, M; Kurzrock, R; Morrison, C
MLA Citation
Zhang, T., et al. “Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients.” Oncoimmunology, vol. 9, no. 1, Jan. 2020. Scopus, doi:10.1080/2162402X.2020.1773200.
URI
https://scholars.duke.edu/individual/pub1449567
Source
scopus
Published In
Oncoimmunology
Volume
9
Published Date
DOI
10.1080/2162402X.2020.1773200

A randomized phase 2 trial of pembrolizumab versus pembrolizumab and acalabrutinib in patients with platinum-resistant metastatic urothelial cancer.

BACKGROUND: Inhibition of the programmed cell death protein 1 (PD-1) pathway has demonstrated clinical benefit in metastatic urothelial cancer (mUC); however, response rates of 15% to 26% highlight the need for more effective therapies. Bruton tyrosine kinase (BTK) inhibition may suppress myeloid-derived suppressor cells (MDSCs) and improve T-cell activation. METHODS: The Randomized Phase 2 Trial of Acalabrutinib and Pembrolizumab Immunotherapy Dual Checkpoint Inhibition in Platinum-Resistant Metastatic Urothelial Carcinoma (RAPID CHECK; also known as ACE-ST-005) was a randomized phase 2 trial evaluating the PD-1 inhibitor pembrolizumab with or without the BTK inhibitor acalabrutinib for patients with platinum-refractory mUC. The primary objectives were safety and objective response rates (ORRs) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Immune profiling was performed to analyze circulating monocytic MDSCs and T cells. RESULTS: Seventy-five patients were treated with pembrolizumab (n = 35) or pembrolizumab plus acalabrutinib (n = 40). The ORR was 26% with pembrolizumab (9% with a complete response [CR]) and 20% with pembrolizumab plus acalabrutinib (10% with a CR). The grade 3/4 adverse events (AEs) that occurred in ≥15% of the patients were anemia (20%) with pembrolizumab and fatigue (23%), increased alanine aminotransferase (23%), urinary tract infections (18%), and anemia (18%) with pembrolizumab plus acalabrutinib. One patient treated with pembrolizumab plus acalabrutinib had high MDSCs at the baseline, which significantly decreased at week 7. Overall, MDSCs were not correlated with a clinical response, but some subsets of CD8+ T cells did increase during the combination treatment. CONCLUSIONS: Both treatments were generally well tolerated, although serious AE rates were higher with the combination. Acalabrutinib plus pembrolizumab did not improve the ORR, PFS, or OS in comparison with pembrolizumab alone in mUC. Baseline and on-treatment peripheral monocytic MDSCs were not different in the treatment cohorts. Proliferating CD8+ T-cell subsets increased during treatment, particularly in the combination cohort. Ongoing studies are correlating these peripheral immunome findings with tissue-based immune cell infiltration.
Authors
Zhang, T; Harrison, MR; O'Donnell, PH; Alva, AS; Hahn, NM; Appleman, LJ; Cetnar, J; Burke, JM; Fleming, MT; Milowsky, MI; Mortazavi, A; Shore, N; Sonpavde, GP; Schmidt, EV; Bitman, B; Munugalavadla, V; Izumi, R; Patel, P; Staats, J; Chan, C; Weinhold, KJ; George, DJ
URI
https://scholars.duke.edu/individual/pub1453944
PMID
32757302
Source
pubmed
Published In
Cancer
Published Date
DOI
10.1002/cncr.33067

Racial Disparity in Response to Prostate Cancer Systemic Therapies.

PURPOSE OF REVIEW: In this review, we aim to describe racial differences in response to treatment for metastatic castration-resistant prostate cancer (mCRPC). RECENT FINDINGS: Recent data suggests that, despite higher risk features, African Americans may respond better than Caucasians to systemic therapies for advanced prostate cancer. This improved response is not limited to one class of drugs but can be seen with androgen-pathway directed therapies, chemotherapy, bone-targeted therapy, and immunotherapy. The mechanisms for this are being further explored. African Americans may respond better to mCRPC treatments but validation in prospective clinical trials is needed.
Authors
Bitting, RL; Goodman, M; George, DJ
MLA Citation
Bitting, Rhonda L., et al. “Racial Disparity in Response to Prostate Cancer Systemic Therapies.Curr Oncol Rep, vol. 22, no. 9, July 2020, p. 96. Pubmed, doi:10.1007/s11912-020-00966-z.
URI
https://scholars.duke.edu/individual/pub1452508
PMID
32700096
Source
pubmed
Published In
Current Oncology Reports
Volume
22
Published Date
Start Page
96
DOI
10.1007/s11912-020-00966-z

Diversity of Enrollment in Prostate Cancer Clinical Trials: Current Status and Future Directions.

BACKGROUND: Although there are considerable racial and ethnic disparities in prostate cancer incidence and mortality in the United States and globally, clinical trials often do not reflect disease incidence across racial and ethnic subgroups. This study aims to comprehensively review the reporting of race and ethnicity data and the representation of race and ethnicity across prostate cancer treatment-, prevention-, and screening-based clinical trials. METHODS: Seventy-two global phase III and IV prevention, screening, and treatment prostate cancer clinical trials with enrollment start dates between 1987 and 2016 were analyzed in this study, representing a total of 893,378 individual trial participants. Availability and representation of race and ethnicity data by trial funding type, temporal changes in the racial/ethnic diversity of participants, and geographic representation of countries were assessed. RESULTS: Of the 72 trials analyzed, 59 (81.9%) had available race data, and 11 (15.3%) of these trials additionally reported ethnicity. Of the trials reporting data, participants were overwhelmingly white men (with the highest proportion in U.S. nonpublicly funded trials), comprising over 96% of the study population. The proportion of white participants in prostate cancer clinical trials has remained at over 80% since 1990. Geographically, Africa and the Caribbean were particularly underrepresented with only 3% of countries included. CONCLUSIONS: Trial participants continue to be majority white despite the known racial disparities in prostate cancer clinical outcomes. IMPACT: Current and future trials must use novel recruitment strategies to ensure enrollment of underrepresented men. Targeting the inclusion of African and Caribbean medical centers is crucial to achieve equity in representation.
Authors
Rencsok, EM; Bazzi, LA; McKay, RR; Huang, FW; Friedant, A; Vinson, J; Peisch, S; Zarif, JC; Simmons, S; Hawthorne, K; Villanti, P; Kantoff, PW; Heath, E; George, DJ; Mucci, LA
MLA Citation
Rencsok, Emily M., et al. “Diversity of Enrollment in Prostate Cancer Clinical Trials: Current Status and Future Directions.Cancer Epidemiol Biomarkers Prev, vol. 29, no. 7, July 2020, pp. 1374–80. Pubmed, doi:10.1158/1055-9965.EPI-19-1616.
URI
https://scholars.duke.edu/individual/pub1447131
PMID
32503813
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Volume
29
Published Date
Start Page
1374
End Page
1380
DOI
10.1158/1055-9965.EPI-19-1616