Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients With Pancreatic Cancer
- Conditions
- Pancreatic Cancer
- Registration Number
- NCT03820921
- Lead Sponsor
- Ponderas Academic Hospital
- Brief Summary
Pancreatic ductal adenocarcinoma (PDAC) has a suboptimal response to standard therapies that modestly impact survival due to its ability to evade host immune surveillance. Emerging evidence has shown that the co-inhibitory receptors, such as programmed death 1 (PD-1), play a critical role in cancer immune-editing. Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. The advent of immunotherapy, with checkpoint inhibitors, which block PD-L1 interaction between tumor cells and activated T cells, has significantly altered the treatment algorithm for several solid tumors.
However, the clinicopathologic significance and prognostic value of PD-L1 in PDAC remains controversial. The main technical ground may be that PDAC PD-L1 expression quantification is limited to surgical resection specimens and dependent on specific immunohistochemistry (IHC) tests. In addition, PD-L1 expression has not been extensively assessed before surgery in treatment-naive PDAC patients, due to the current IHC test requirement for a histologic rather than a cytologic evaluation. However, a recent study showed that EUS-fine needle biopsy (FNB) can successfully determine primary pancreas malignancy PD-L1 status.
One recently identified subtype within the genomic landscape of PDAC is the mismatch repair-deficient (dMMR) tumor. Evaluation of dMMR status is particularly important following the FDA approval of the PD-1 inhibitor, pembrolizumab, for the treatment of unresectable or metastatic, microsatellite instability-high (MSI-H) or dMMR PDAC that have progressed following prior treatment, and have no satisfactory alternative treatment options.
The objectives of the project will include the assessment of tumor PD-L1/dMMR expression in patients with PDAC using EUS-FNB samples and the prospective correlation of MMR status and PD-L1 expression with overall survival and progression-free survival of PDAC patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
Not provided
-previous chemotherapy or radiotherapy
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Feasibility of PD-L1 expression analysis on EUS-FNB pancreatic specimens 1 year the percentage of cases where EUS-FNB material was adequate to determine PDL-1 expression
Feasibility of MMR status analysis on EUS-FNB pancreatic specimens 1 year the percentage of cases where EUS-FNB material was adequate to determine MMR status
- Secondary Outcome Measures
Name Time Method Tumor response 3 months Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). According to RECIST guidelines,complete response (CR) is defined as the complete disappearance of the tumor, partial response (PR) as ≥30% decrease in longest diameter (LD), progressive disease (PD) as ≥20% increase in LD, and stable disease (SD) as a decrease or increase less than PR or PD based on anatomic assessment. Patients with CR or PR will be defined as responders, whereas those with PD or SD are defined as non-responders.
Overall survival up to 12 months The overall survival will be measured from the day of diagnosis to the date of death
Progression-free survival up to 12 months The progression-free survival (PFS) will be measured from the day of diagnosis to the date of progressive disease.