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

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

BAYER PROTOTYPE PROSTATE PROGRAM - 3 DAY PROGRAMMING

Administered By
Medicine, Medical Oncology
Awarded By
Bayer Healthcare Pharmaceuticals Inc
Role
Principal Investigator
Start Date
End Date

Publications:

Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab.

The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed to retrospectively identify all patients with mRCC treated with I+N in the Duke Cancer Institute and the Cleveland Clinic Taussig Cancer Center, followed by a chart review. Patients were included if they had BrM at the time of I+N initiation. Cohort characteristics are summarized with descriptive statistics. Kaplan-Meier method was used to estimate overall survival (OS) and global, intracranial, and extracranial progression-free survival (PFS) for the cohort and log rank test was used to compare OS and PFS between patient groups. Radiographic response was categorized by RECIST. Fisher's exact test was used to correlate patient factors with radiographic response. From October 2017 to December 2020, 19 patients with BrM received I+N for mRCC with a median follow-up time of 27.1 months (range 15.0-35.6). By International Metastatic RCC Database Consortium (IMDC) risk criteria, 16% had favorable, 58% had intermediate, and 26% had poor-risk disease. 68% were systemic therapy naïve, and 77% of patients had clear cell histology. 95% had received local CNS directed therapy with surgery, radiotherapy, or both. The objective response rate was 44% (0% complete response) with three of six patients treated in the second line or greater setting experiencing a partial response. The median PFS was 7.6 months (95% CI 5.6 to 14.9). The median extracranial PFS was 8.5 months (95% CI 5.6 to 19.7), and median intracranial PFS was 14.7 months (95% CI 7.2 to not reached). No variables assessed were significantly associated with radiographic response (gender, IMDC risk, presence of bone metastasis, line of therapy, or presence of immune related adverse events). In our retrospective cohort of patients with mRCC with BrM, I+N, in combination with CNS-directed local therapy, appears to have clinical efficacy as previously described with responses seen beyond the first-line setting. Further investigation is warranted in this population given exclusion from prior clinical trials.
Authors
Brown, LC; Desai, K; Wei, W; Kinsey, EN; Kao, C; George, DJ; Rini, BI; Ornstein, MC; Zhang, T
MLA Citation
Brown, Landon C., et al. “Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab.J Immunother Cancer, vol. 9, no. 9, Sept. 2021. Pubmed, doi:10.1136/jitc-2021-003281.
URI
https://scholars.duke.edu/individual/pub1497328
PMID
34518292
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
9
Published Date
DOI
10.1136/jitc-2021-003281

Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma.

BACKGROUND: In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS) and overall survival (OS) versus everolimus in patients with advanced RCC after prior antiangiogenic therapy. METHODS: In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods. For on-treatment changes, PFS and OS were analyzed using fold change in biomarker levels at week 4. Biomarkers were considered prognostic if p < 0.05 and predictive if pinteraction < 0.05 for the interaction between treatment and biomarker. RESULTS: Hazard ratios for PFS and OS favored cabozantinib versus everolimus for both low and high baseline levels of all biomarkers (hazard ratios ≤0.78). In univariate analyses, low baseline HGF, AXL, and VEGF were prognostic for improvements in both PFS and OS with cabozantinib, and low HGF was prognostic for improvements in both PFS and OS with everolimus. Low AXL was predictive of relative improvement in PFS for cabozantinib versus everolimus. Results were generally consistent when baseline biomarkers were expressed as continuous variables, although none were predictive of benefit with treatment. In multivariable analysis, low baseline HGF was independently prognostic for improved PFS for both cabozantinib and everolimus; low HGF, GAS6, and VEGF were independently prognostic for improved OS with cabozantinib. No biomarkers were independently prognostic for OS with everolimus. On-treatment increases in some biomarkers appeared prognostic for PFS or OS with cabozantinib in univariate analyses; however, none were independently prognostic in multivariable analysis. CONCLUSIONS: PFS and OS were improved with cabozantinib versus everolimus at high and low baseline levels of all biomarkers. Low baseline HGF was consistently identified as a prognostic biomarker for improved PFS or OS with cabozantinib or everolimus, supporting further prospective evaluation of the prognostic significance of HGF in advanced RCC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01865747 (registered on 05/31/2013).
Authors
Powles, T; Choueiri, TK; Motzer, RJ; Jonasch, E; Pal, S; Tannir, NM; Signoretti, S; Kaldate, R; Scheffold, C; Wang, E; Aftab, DT; Escudier, B; George, DJ
MLA Citation
Powles, Thomas, et al. “Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma.Bmc Cancer, vol. 21, no. 1, 2021, p. 904. Pubmed, doi:10.1186/s12885-021-08630-w.
URI
https://scholars.duke.edu/individual/pub1289632
PMID
34364385
Source
pubmed
Published In
Bmc Cancer
Volume
21
Published Date
Start Page
904
DOI
10.1186/s12885-021-08630-w

A Prospective Multicenter Evaluation of Initial Treatment Choice in Metastatic Renal Cell Carcinoma Prior to the Immunotherapy Era: The MaRCC Registry Experience.

INTRODUCTION: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). METHODS AND MATERIALS: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations. RESULTS: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8-not reached] months) versus pazopanib (39.0 [29.7-50.9] months) and sunitinib 26.2 [19.9-61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs. 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection. CONCLUSION: The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints.
Authors
Costello, BA; Bhavsar, NA; Zakharia, Y; Pal, SK; Vaishampayan, U; Jim, H; Fishman, MN; Molina, AM; Kyriakopoulos, CE; Tsao, C-K; Appleman, LJ; Gartrell, BA; Hussain, A; Stadler, WM; Agarwal, N; Pachynski, RK; Hutson, TE; Hammers, HJ; Ryan, CW; Mardekian, J; Borham, A; George, DJ; Harrison, MR
MLA Citation
Costello, Brian A., et al. “A Prospective Multicenter Evaluation of Initial Treatment Choice in Metastatic Renal Cell Carcinoma Prior to the Immunotherapy Era: The MaRCC Registry Experience.Clin Genitourin Cancer, July 2021. Pubmed, doi:10.1016/j.clgc.2021.07.002.
URI
https://scholars.duke.edu/individual/pub1493276
PMID
34364796
Source
pubmed
Published In
Clin Genitourin Cancer
Published Date
DOI
10.1016/j.clgc.2021.07.002

Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.

Authors
Armstrong, AJ; Nixon, AB; Carmack, A; Yang, Q; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Hainsworth, JD; Kollmannsberger, CK; Logan, TF; Puzanov, I; Pickering, LM; Ryan, CW; Protheroe, A; George, DJ; Halabi, S
MLA Citation
Armstrong, Andrew J., et al. “Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.Clin Cancer Res, vol. 27, no. 12, June 2021, p. 3503. Pubmed, doi:10.1158/1078-0432.CCR-21-1636.
URI
https://scholars.duke.edu/individual/pub1486354
PMID
34117029
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
3503
DOI
10.1158/1078-0432.CCR-21-1636

Real-World Utilization of Oral Anticancer Agents and Related Costs in Older Adults with Metastatic Renal Cell Carcinoma in the United States.

BACKGROUND: Substantial racial and socioeconomic disparities in metastatic RCC (mRCC) have persisted following the introduction of targeted oral anticancer agents (OAAs). The relationship between patient characteristics and OAA access and costs that may underlie persistent disparities in mRCC outcomes have not been examined in a nationally representative patient population. METHODS: Retrospective SEER-Medicare analysis of patients diagnosed with mRCC between 2007-2015 over age 65 with Medicare part D prescription drug coverage. Associations between patient characteristics, OAA receipt, and associated costs were analyzed in the 12 months following mRCC diagnosis and adjusted to 2015 dollars. RESULTS: 2,792 patients met inclusion criteria, of which 32.4%received an OAA. Most patients received sunitinib (57%) or pazopanib (28%) as their first oral therapy. Receipt of OAA did not differ by race/ethnicity or socioeconomic indicators. Patients of advanced age (> 80 years), unmarried patients, and patients residing in the Southern US were less likely to receive OAAs. The mean inflation-adjusted 30-day cost to Medicare of a patient's first OAA prescription nearly doubled from $3864 in 2007 to $7482 in 2015, while patient out-of-pocket cost decreased from $2409 to $1477. CONCLUSION: Race, ethnicity, and socioeconomic status were not associated with decreased OAA receipt in patients with mRCC; however, residing in the Southern United States was, as was marital status. Surprisingly, the cost to Medicare of an initial OAA prescription nearly doubled from 2007 to 2015, while patient out-of-pocket costs decreased substantially. Shifts in OAA costs may have significant economic implications in the era of personalized medicine.
Authors
Wilson, LE; Spees, L; Pritchard, J; Greiner, MA; Scales, CD; Baggett, CD; Kaye, D; George, DJ; Zhang, T; Wheeler, SB; Dinan, MA
MLA Citation
Wilson, Lauren E., et al. “Real-World Utilization of Oral Anticancer Agents and Related Costs in Older Adults with Metastatic Renal Cell Carcinoma in the United States.Kidney Cancer, vol. 5, no. 3, 2021, pp. 115–27. Pubmed, doi:10.3233/KCA-210119.
URI
https://scholars.duke.edu/individual/pub1496387
PMID
34632169
Source
pubmed
Published In
Kidney Cancer
Volume
5
Published Date
Start Page
115
End Page
127
DOI
10.3233/KCA-210119