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Hepato-pancreato-biliary

E198: Analysis of Extracellular Vesicle Protein Profiles to Predict Treatment Response in a Phase II Clinical Trial with Cabozantinib and Pembrolizumab for Refractory Metastatic Pancreatic Cancer

    ePoster Abstract Author(s)

  • Hannah G. McDonald, MD

    General Surgery Resident
    Department of Surgery, University of Kentucky
    Lexington, Kentucky, United States

    • Submitter(s)

  • Hannah G. McDonald, MD

    General Surgery Resident
    Department of Surgery, University of Kentucky
    Lexington, Kentucky, United States

    • Author(s)

  • Hannah G. McDonald, MD

    General Surgery Resident
    Department of Surgery, University of Kentucky
    Lexington, Kentucky, United States

  • AR

    Anna Reagan, MD

    General Surgery Resident
    Department of Surgery, University of Kentucky, United States

  • RP

    Reema A. Patel, MD

    Medical Oncologist
    Department of Internal Medicine, University of Kentucky, United States

  • JM

    Jessica Moss, MD

    Medical Oncologist
    Department of Internal Medicine, University of Kentucky, United States

  • SN

    Snigdha Nutalapati, MD

    Medical Oncologist
    Department of Internal Medicine, University of Kentucky, United States

  • Michael J. Cavnar, MD

    Surgical Oncologist
    Division of Surgical Oncology, Department of Surgery, University of Kentucky
    Lexington, Kentucky, United States

  • Prakash K. Pandalai, MD (he/him/his)

    Surgical Oncologist
    Division of Surgical Oncology, Department of Surgery, University of Kentucky, United States

  • MB

    Mautin Barry-Hundeyin, MD

    Surgical Oncologist
    Division of Surgical Oncology, Department of Surgery, University of Kentucky, United States

  • TC

    Teresa Cassel, BS

    Research Coordinator
    Department of Toxicology, University of Kentucky Markey Cancer Center, United States

  • AL

    Andrew Lane, PhD

    Principal Investigator
    Department of Toxicology, University of Kentucky Markey Cancer Center, United States

  • RH

    Richard Higashi, PhD

    Principal Investigator
    Department of Toxicology, University of Kentucky Markey Cancer Center, United States

  • TF

    Teresa Fan, PhD

    Principal Investigator
    Department of Toxicology, University of Kentucky Markey Cancer Center, United States

  • JK

    Joseph Kim, MD

    Professor and Chief of Surgical Oncology
    Division of Surgical Oncology, Department of Surgery, University of Kentucky, Kentucky, United States

Introduction:

Real-time monitoring of treatment response is a major barrier in the care of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Our prior studies revealing PD1-mediated activation of the proto-oncogene MET resulted in the development of an investigator-initiated phase II clinical trial for mPDAC patients (NCT05052723). Our groups also discovered discrete extracellular vesicle (EV) protein payloads in PDAC patients, we thus sought to assess the utility of EV proteins as novel candidate markers for predicting drug efficacy in a phase II clinical trial.

Methods:

Inclusion criteria was for mPDAC patients with disease progression on standard of care therapy. Treatment regimen consisted of (anti-PD1) pembrolizumab (200 mg) every 3 weeks and (anti-MET) cabozantinib (40 mg) PO daily until radiographic evidence of disease progression. Plasma was collected from study participants before and at designated timepoints during treatment. EVs were isolated from patient plasma using size exclusion chromatography. Proteins and lipids were then extracted from EVs and characterized using reverse-phase protein array (RPPA) and mass spectrometry, respectively.

Results:

We have accrued a total of 20 patients. To date, 15 patients have completed treatment and 11 have undergone plasma analysis of EV protein payloads.  Of the 23 candidate protein markers with known PDAC association, 8 markers including STAT3, TIM3, ZIP4, ERBB2, EPCAM, ALPP, CD171, and CEA increased > 50% with disease progression. 7 of these  simultaneously decreased > 50% with treatment response in 1 patient (Figure). Interestingly, three patients did not show elevation of the PDAC tumor marker (CA 19-9) despite disease progression but did show increased EV protein markers.

Conclusions:

Methodology to detect progression on treatment prior to standard imaging is imperative, particularly for patients with refractory advanced disease. We show consistent trends in multiple EV protein payloads which may aid in early detection of progression while on therapy. Future directions include more targeted analysis of these candidate protein markers as well as EV lipid analysis after the completion of accrual.

Learning Objectives:

  • Consider the utility of extracellular vesicle protein loads to detect or predict treatment response in patients with advanced malignancies.
  • Describe the necessity of collaborative relationships to translate research from patient/trial, to the bench, and back to clinical decision-making.
  • Discuss the utility of plasma-based metabolomic studies in patients with metastatic pancreatic cancer.