Biomarkers, targeted and immunotherapies for pancreatic cancer

This section covers the following topics:

• Genetic testing for inherited mutations for treatment selection
• Tumor biomarker testing for treatment selectior 
• PARP inhibitors
• Immunotherapy
• Other targeted therapy

Genetic tests for inherited mutations for treatment selection

Any person diagnosed with pancreatic cancer meets national guidelines for genetic testing for an inherited mutation. Genetic testing may be used to guide treatment selection.  

• People who test positive for an inherited BRCA1 or BRCA2 mutation may respond better to a treatment regimen that includes a type of chemotherapy known as platinum. They may also benefit from maintenance therapy with a type of targeted therapy known as a PARP inhibitor.  
• People who test positive for other inherited gene mutations may qualify for clinical trials looking at targeted therapies. 
• People who test positive for a Lynch syndrome gene mutation may benefit from treatment with an immunotherapy agent. 

Biomarker testing for treatment selection

Biomarker tests look at samples of blood, tumor or other tissue for changes or abnormalities caused by cancer. These tests can give doctors clues about the cancer, including:

• how fast the cancer is growing
• which treatments are most likely to work
• whether or not the cancer is responding to treatment or growing
• whether or not the cancer has come back after remission

Biomarker tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. Biomarker tests used to select a specific treatment are sometimes called "companion diagnostic tests." These tests may be done on tumor tissue or (in many cases) on blood. See our Biomarker Testing section for more information. 

Examples of biomarker tests used in pancreatic cancer include:

• Some pancreatic cancers will have an abnormality known as MSI-H (“microsatellite instability high") also known as "mismatch repair deficiency" (dMMR or MMR-D). MSI-H cancers are common in people with a Lynch syndrome gene mutation. These cancers may respond well to a type of treatment known as an immune checkpoint inhibitor. One example of an immunotherapy agent used for MSI-high cancers is Keytruda (pembrolizumab).
• Some cancers have a specific genetic change called an NTRK fusion, which can be found on tumor testing. People whose tumor test reveals an NTRK fusion may benefit from the targeted therapy Vitrakvi (larotrectinib).
• Additional biomarker tests may help identify people who are elegible for certain clinical trials. 

PARP inhibitors 

PARP inhibitors work by blocking a protein used by cells to repair damaged DNA. They were initially developed to treat cancers in people with an inherited gene mutation BRCA1 or BRCA2 mutation. For people with pancreatic cancer, the PARP inhibitor Lynparza (olaparib) has been approved as maintenance therapy in patients with advanced pancreatic cancer whose cancer has stabilized after at least four months of chemotherapy.  Approximately 5-8% of patients with pancreatic cancers will have a mutation in BRCA or related genes.

Research is ongoing to learn if PARP inhibitors are also affective for treating cancer in other situations, including:  

• people with an inherited mutation in a different gene that repairs DNA damage (for example: PALB2).
• people who do not have an inherited gene mutation, but their tumor tested positive for an acquired mutation in a gene that repairs DNA damage.
• in combination with immunotherapy or other agents.

Immunotherapies 

Immunotherapies are cancer treatments that hlep the body’s immune system detect and attack cancer cells. There are several different categories of immunotherapies. 

• Keytruda (pembrolizumab) is known as an immune checkpoint inhibitor. Keytruda is approved for treatment of patients with metastatic cancer with a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Although this biomarker is not common in pancreatic cancer, it is often seen in people with a Lynch syndrome gene mutation who develop cancer. 

Other targeted therapies

• Tarceva (erlotinib) is approved in combination with the chemotherapy gemcitabine as first-line therapy for locally advanced, unresectable or metastatic pancreatic cancer.  
• Vitrakvi (larotrectinib) is approved for treatment of pancreatic cancer that is metastatic or cannot be removed with surgery and has worsened with other treatments. It targets a specific genetic change called an NTRK fusion. This type of genetic change is found in a range of cancers, including pancreatic cancer.
• Afinitor (everolimus) is a type of targeted therapy known as an mTOR inhibitor that is FDA approved for treating people with advanced pancreatic neuroendocrine tumors.
• Sutent is a targeted therapy that is FDA approved to treat patients with pancreatic neuroendocrine tumors that cannot be removed by surgery or that have metastasized.

Table of targeted and immunotherapies for pancreatic cancer