Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients With Pancreatic Cancer (SUCCESS)

Ponderas Academic Hospital

Status: Unknown

Conditions: Pancreatic Cancer

Treatments: Diagnostic Test: EUS-FNB; Other: Immunohistochemistry

Study type: Observational

Funder types: Other

Identifiers

NCT03820921

SUCCESS

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Age 18 to 90 years old
• men or women
• signed informed consent for EUS and EUS -FNB
• the diagnosis of adenocarcinoma histologically confirmed by FNB
• resectable, Unresectable, locally advanced and/or metastatic disease

Exclusion Criteria:

-previous chemotherapy or radiotherapy

Trial design

30 participants in 1 patient group

PATIENTS WITH PANCREATIC CANCER

Description:

All patients with a suspicion of pancreatic masses will undergo EUS (including EUS-FNB for confirmation of diagnosis). A positive cytological diagnosis will be taken as a final proof of malignancy of the pancreas mass. The diagnoses obtained by EUS-FNB will be further verified during a clinical follow-up of at least 6 months. Immunochemistry will be performed on the EUS-FNB specimens to determine PD-L1 expression and MMR status

Treatment:

Other: Immunohistochemistry

Diagnostic Test: EUS-FNB