James Abbruzzese

Overview:

My research interests include the clinical study and treatment of pancreatic cancer.

Positions:

D. C. I. Distinguished Professor of Medical Oncology

Medicine, Medical Oncology
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Chief, Division of Medical Oncology

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1978

The University of Chicago

Intern, Internal Medicine

Johns Hopkins University School of Medicine

Resident, Internal Medicine

Johns Hopkins University School of Medicine

Grants:

Topic Refinement, Task order 9 Topic Briefs

Administered By
Duke Clinical Research Institute
Awarded By
Patient Centered Outcomes Research Institute
Role
Co Investigator
Start Date
End Date

Pfizer - C4201002 - PF-07265807

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

A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS

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

Publications:

Blood-based biomarkers in patients with platinum-sensitive and resistant ovarian cancer treated with olaparib and cediranib: results from the UM9825 trial

Authors
Nixon, A; Liu, J; Xiong, N; Hurwitz, HI; Lyu, J; Liu, Y; Starr, M; Brady, J; Swisher, E; Owzar, K; Wenham, R; Hendrickson, AW; Armstrong, D; Chan, N; Cohn, D; Lee, J-M; Penson, R; Cristea, M; Gaillard, S; Abbruzzese, J; Matsuo, K; Olawaiye, A; Kohn, E; Ivy, P; Secord, AA
URI
https://scholars.duke.edu/individual/pub1496553
Source
wos-lite
Published In
Gynecologic Oncology
Volume
162
Published Date
Start Page
S99
End Page
S99

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience.

Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB). PATIENTS AND METHODS: MRT is an internally developed system that aggregates and normalizes genomic profiling results from multiple sources. MRT serves as the foundation for our MTB, a team that reviews genomic results for all Duke University Health System cancer patients, provides notifications for targeted therapies, matches patients to biomarker-driven trials, and monitors the molecular landscape of tumors at our institution. RESULTS: Among 215 patients reviewed by our MTB over a 6-month period, we identified 176 alterations associated with therapeutic sensitivity, 15 resistance alterations, and 51 alterations with potential germline implications. Of reviewed patients, 17% were subsequently treated with a targeted therapy. For 12 molecular therapies approved during the course of this work, we identified between two and 71 patients who could qualify for treatment based on retrospective MRT data. An analysis of 14 biomarker-driven clinical trials found that MRT successfully identified 42% of patients who ultimately enrolled. Finally, an analysis of 4,130 comprehensive genomic profiles from 3,771 patients revealed that the frequency of clinically significant therapeutic alterations varied from approximately 20% to 70% depending on the tumor type and sequencing test used. CONCLUSION: With robust informatics tools, such as MRT, and the right MTB structure, a precision cancer medicine program can be developed, which provides great benefit to providers and patients with cancer.
Authors
Green, MF; Bell, JL; Hubbard, CB; McCall, SJ; McKinney, MS; Riedel, JE; Menendez, CS; Abbruzzese, JL; Strickler, JH; Datto, MB
MLA Citation
URI
https://scholars.duke.edu/individual/pub1497103
PMID
34568718
Source
pubmed
Published In
Jco Precision Oncology
Volume
5
Published Date
DOI
10.1200/PO.21.00030

Durvalumab, Tremelimumab Alone or in Combination With Low-Dose or Hypofractionated Targeted Radiotherapy in Metastatic Non-Small Cell Lung Cancer Refractory to Prior PD-1 Therapy: A Multicentre, Open-Label, Randomized, Phase 2 Trial

Authors
Schoenfeld, JD; Giobbie-Hurder, A; Ranasinghe, S; Kao, KZ; Lako, A; Tsuji, J; Liu, Y; Brennick, RC; Gentzler, R; Lee, C; Hubbard, J; Abbruzzese, JL; Jabbour, SK; Uboha, N; Stephans, K; Johnson, JM; Park, H; Villaruz, LC; Sharon, E; Streicher, H; Ahmed, M; Lyon, H; Cibuskis, C; Lennon, N; Jhaveri, A; Yang, L; Altreuter, J; Gunasti, L; Weirather, JL; Mak, RH; Awad, MM; Rodig, SJ; Chen, HX; Wu, CJ; Monjazeb, AM; Hodi, FS
URI
https://scholars.duke.edu/individual/pub1498640
Source
ssrn

A case report of microsatellite instability (MSI)-high, <i>HER2</i> amplified pancreatic adenocarcinoma with central nervous system metastasis.

Pancreatic adenocarcinoma commonly presents as metastatic disease and harbors a dire prognosis due to its aggressive behavior, propensity for resistance to therapies, and lack of targetable driver mutations. Additionally, despite advances in other cancers, immunotherapy has been ineffective in this disease thus far and treatment remains centered around cytotoxic chemotherapy. Here, we present a case of a patient with pancreatic adenocarcinoma harboring both high microsatellite instability (MSI-H) and <i>HER2</i> amplification. After an initial response to standard-of-care chemotherapy with FOLFIRINOX followed by progression, she was treated with dual immune checkpoint blockade, which resulted in a period of disease control. This was complicated by the development of autoimmune hypophysitis and an incidental finding of brain metastasis on magnetic resonance imaging (MRI). Her extracranial disease progressed while receiving stereotactic radiosurgery, with findings of lymphangitic spread in her lungs, and her treatment was changed to gemcitabine/nab-paclitaxel with trastuzumab. This resulted in a degree of extracranial disease control, though she experienced progressive brain metastases despite radiation and therapeutic switch to lapatinib and trastuzumab. Ultimately, the patient developed leptomeningeal disease which was not controlled by intrathecal trastuzumab. Given the rarity of central nervous system metastasis, <i>HER2</i> amplification, and MSI in pancreatic cancer, this patient's presentation represents a confluence of multiple unique features. This case highlights the clinical value of up-front next-generation sequencing in metastatic pancreatic cancer and the ability of pancreatic cancer with actionable molecular variants to develop atypical sites of disease and adaptive resistance.
MLA Citation
DeVito, Nicholas C., et al. “A case report of microsatellite instability (MSI)-high, HER2 amplified pancreatic adenocarcinoma with central nervous system metastasis.Ame Case Reports, vol. 5, Jan. 2021, p. 14. Epmc, doi:10.21037/acr-20-154.
URI
https://scholars.duke.edu/individual/pub1481212
PMID
33912803
Source
epmc
Published In
Ame Case Reports
Volume
5
Published Date
Start Page
14
DOI
10.21037/acr-20-154

Targeting the IL-2 inducible kinase in melanoma; a phase 2 study of ibrutinib in systemic treatment-refractory distant metastatic cutaneous melanoma: preclinical rationale, biology, and clinical activity (NCI9922).

BACKGROUND: IL-2 inducible kinase (ITK) is highly expressed in metastatic melanomas and its inhibition suppresses melanoma cell proliferation. We hypothesize that ibrutinib has a direct antitumor effect in melanoma cell lines and that treatment of metastatic melanomas with ibrutinib induces antitumor responses. METHODS: We assessed the ibrutinib effect on melanoma cell proliferation, apoptosis, and motility. Patients with metastatic melanoma refractory to PD-1 and MAPK inhibitors (if BRAFV600-mutant) were treated with ibrutinib, 840 mg PO QD, as part of a phase II clinical trial (clinicaltrials.gov NCT02581930). RESULTS: Melanoma cell lines frequently express ITK, YES1, and EGFR. Ibrutinib suppressed cell motility and proliferation in most cell lines. Eighteen patients (13 male; median age 63.5 years, range 37-82; 12 with ipilimumab resistance) were enrolled. The most frequent side effects were fatigue (61%), anorexia (50%), hyponatremia (28%), nausea, and vomiting (22% each). No antitumor responses were seen. At a median follow-up of 6 months (0.3-35.8 months), the median progression-free survival was 1.3 months (range 0.2-5.5 months). Fifteen patients were discontinued from the study due to progression, and 14 patients had died from metastatic melanoma. All archived tumors expressed ITK, 41% had no expression of p16 and PTEN, and 61% had absent tumor-infiltrating lymphocytes (TILs). Ibrutinib significantly suppressed proliferating (Ki67+) CD19+ peripheral blood mononuclear cells and had no significant effect on other lymphocyte subsets. CONCLUSION: Ibrutinib did not induce any meaningful clinical benefit. ITK expression may not be clinically relevant. Treatment-refractory metastatic melanomas have other fundamental defects (i.e. absent PTEN and p16 expression, absent TILs) that may contribute to an adverse prognosis.
Authors
Moschos, SJ; Eroglu, Z; Khushalani, NI; Kendra, KL; Ansstas, G; In, GK; Wang, P; Liu, G; Collichio, FA; Googe, PB; Carson, CC; McKinnon, K; Wang, H-H; Nikolaishvilli-Feinberg, N; Ivanova, A; Arrowood, CC; Garrett-Mead, N; Conway, KC; Edmiston, SN; Ollila, DW; Serody, JS; Thomas, NE; Ivy, SP; Agrawal, L; Dees, EC; Abbruzzese, JL
MLA Citation
URI
https://scholars.duke.edu/individual/pub1476134
PMID
33661190
Source
pubmed
Published In
Melanoma Res
Volume
31
Published Date
Start Page
162
End Page
172
DOI
10.1097/CMR.0000000000000726

Research Areas:

Adolescent
Adult
Age Distribution
Albumins
Animals
Blood Transfusion
Cell Differentiation
Cell Growth Processes
Cell Lineage
Cell Movement
Cell Transformation, Neoplastic
Chemotherapy, Adjuvant
Chi-Square Distribution
Child
Cisplatin
Clinical Competence
Combined Modality Therapy
Cytokines
DNA Repair
Diabetes Complications
Diabetes Mellitus, Type 2
Diagnosis, Differential
Disease Models, Animal
Disease-Free Survival
Drug Delivery Systems
Drug Therapy, Combination
Dyspnea
Epithelial Cells
False Positive Reactions
Fibrosis
Genetic Variation
Genotype
HEK293 Cells
HT29 Cells
Health Status
Homozygote
Hypothyroidism
Immunohistochemistry
Inflammation
Intercellular Signaling Peptides and Proteins
Islets of Langerhans
Isotope Labeling
Liver
Liver Neoplasms
Liver Neoplasms, Experimental
Lymph Nodes
Membrane Proteins
Mesoderm
Models, Biological
Mutation
Neoadjuvant Therapy
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasms
Nervous System
Odds Ratio
Organoplatinum Compounds
Oxidative Stress
Pain
Pancreas
Pancreatectomy
Pancreatic Ducts
Pancreatic Neoplasms
Pancreaticoduodenectomy
Patient Care Team
Phenotype
Physicians
Polymorphism, Genetic
Probability
Prognosis
Proteolysis
Pyrimidines
Quinazolines
Radiation Tolerance
Radiotherapy, Adjuvant
Reactive Oxygen Species
Reference Values
Reproducibility of Results
Risk
Sensitivity and Specificity
Sepsis
Sex Distribution
Signal Transduction
Thiazoles
Time Factors
Treatment Outcome
Tumor Cells, Cultured
Tumor Markers, Biological
Water
Xenograft Model Antitumor Assays