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Quantification of PD-L1 expression and tumor mutational burden in biologically distinct advanced pancreatic cancers
Kevin Y Li1,2, Andrew M Lowy1,2, Paul Fanta2,3
1Department of Surgery, Division of Surgical Oncology, University of California, San Diego, San Diego, CA, United States.
Background:
The advent of checkpoint therapy is one of the most important recent advancements in cancer therapy. Though checkpoint therapy is a mainstay in some cancers, it has been largely ineffective in treating cancers of the pancreas. Pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors are seldom responsive to checkpoint inhibition.
Case Presentations:
Here we present two cases of advanced pancreatic cancers that either failed to respond or recurred following conventional treatments. Tissue from each tumor was sequenced and analyzed for PD-L1 expression. Each patient was started on checkpoint blockade after assessing for a predictive biomarker, either the combined positive score or the tumor mutational burden. In each case, checkpoint blockade led to durable radiographic responses.
Conclusions:
We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.
Insights
Checkpoint blockade shows promise for advanced pancreatic cancers that resist conventional treatments. Assessing biomarkers like combined positive score and tumor mutational burden may guide effective immunotherapy strategies.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Checkpoint therapy is a significant advancement in cancer treatment but shows limited efficacy in pancreatic cancers.
- Pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors are generally unresponsive to checkpoint inhibition.
Observation:
- Two cases of advanced pancreatic cancer with treatment resistance or recurrence were analyzed.
- Tumor tissue was sequenced for PD-L1 expression, and predictive biomarkers (combined positive score, tumor mutational burden) were assessed.
- Patients received checkpoint blockade therapy based on biomarker assessment.
Findings:
- Checkpoint blockade therapy resulted in durable radiographic responses in both patients with advanced pancreatic cancer.
- The study highlights potential efficacy in previously refractory or recurrent pancreatic tumors.
Implications:
- Biomarker assessment (combined positive score, tumor mutational burden) is proposed for selecting patients with refractory or recurrent pancreatic cancer for checkpoint blockade therapy.
- This approach may improve outcomes for pancreatic cancer patients who have exhausted conventional treatment options.
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