Targeted therapy for pancreatic cancer

Targeted therapy uses drugs to target specific molecules (such as proteins) or molecular changes on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy. Targeted therapy is sometimes used to treat pancreatic cancer. If you have targeted therapy, your healthcare team will use what they know about the cancer and about your health to plan the drugs, doses and schedules.

You may have targeted therapy to:

• treat unresectable or recurrent pancreatic cancer
• treat pancreatic cancer that doesn't respond to other treatments or comes back (recurs) after treatment

The type of targeted therapy given depends on the type of gene mutation that genetic testing found during diagnosis. These mutations can be inherited or spontaneous in the tumour cells. Based on the results of genetic testing, there are many types of targeted therapy that your healthcare team may consider offering.

Unfortunately, genetic testing is not available at all cancer centres and hospitals in Canada. Targeted therapy is not offered at centres and hospitals where genetic testing is unavailable.

If you had genetic testing and your healthcare team thinks you may benefit from a targeted therapy drug, they will talk to you about your options to pay for it as targeted therapy drugs may not be covered by all provincial or territorial health plans.

Poly-ADP ribose polymerase (PARP) inhibitors are drugs that block PARP proteins. PARP is an enzyme that helps repair damage to DNA. By blocking PARP, cancer cells can’t repair their DNA, which causes them to die.

Olaparib (Lynparza) is a PARP inhibitor that may be used to treat pancreatic cancer if you have a BRCA1/2 or PALB mutation. BRCA1/2 and PALB mutations are the most common inherited mutations in people with pancreatic cancer.

Olaparib is taken as a pill by mouth (orally) once daily.

Neurotrophic tyrosine receptor kinase (NTRK) inhibitors are drugs that block NTRK proteins.

The NTRK gene tells nerve cells to make a protein that helps them send information about certain bodily sensations. When part of the NTRK gene breaks off and joins with another gene, it is called an NTRK gene fusion. This change causes abnormal proteins called TRK fusion proteins, which may cause cancer cells to grow.

NTRK inhibitors that may be used to treat unresectable, metastatic or recurrent pancreatic cancer that has an NTRK gene fusion mutation include:

• larotrectinib (Vitrakvi)
• entrectinib (Rozlytrek)

Larotrectinib and entrectinib are taken orally once daily.

BRAF inhibitors are drugs that block the B-Raf protein. B-Raf sends signals to other cell proteins, such as MEK proteins, to help the cell grow. Mitogen-activated protein kinase kinase (MEK) inhibitors block MEK proteins.

Sometimes, pancreatic cancer has a mutation in the BRAF gene. This mutation causes an increase in B-Raf activity, which can cause cancer cells to grow. By blocking B-Raf or MEK in pancreatic cancer with a BRAF gene mutation, the cancer cells are unable to grow and divide.

Dabrafenib (Tafinlar), a BRAF inhibitor, and trametinib (Mekinist), a MEK inhibitor, may be used to treat unresectable, metastatic or recurrent pancreatic cancer with a BRAF mutation. Dabrafenib and trametinib are taken orally once daily.

KRAS inhibitors are drugs that block the K-Ras protein. K-Ras sends signals to cells to help them grow and divide.

When pancreatic cancer has a mutation in the KRAS gene, such as KRAS G12C, it causes an increase in K-Ras activity and an increase in cancer cell growth and division. By blocking K-Ras in pancreatic cancer with a KRAS gene mutation, the cancer cells are unable to grow and divide.

Sotorasib (Lumakras) is a KRAS inhibitor that may be given for unresectable, metastatic or recurrent pancreatic cancer with a KRAS mutation. It is taken orally once daily.

RET inhibitors are drugs that block the RET kinase protein.

When part of the RET gene breaks off and joins with another gene, it is called a RET gene fusion. This change causes abnormal RET kinase proteins, which tell cells to never stop growing and dividing.

Selpercatinib (Retevmo) is a RET inhibitor that may be used to treat unresectable, metastatic or recurrent pancreatic cancer that has a RET gene fusion mutation. It is taken orally once daily.

Researchers are actively looking into whether other types of targeted therapy are useful to treat pancreatic cancer with certain gene mutations. Your healthcare team may offer you a drug to treat pancreatic cancer that is not listed on this page or is usually given for a different type of cancer (called off-label use). If they think another type of targeted therapy may help you, they will talk to you about how the therapy works and any side effects it may cause.

Some drugs are not yet available in Canada except for patients in a clinical trial. If you have unresectable, metastatic or recurrent pancreatic cancer that cannot be treated with another drug, your healthcare team may recommend a clinical trial for a new targeted therapy drug.

For example, if you have the rare KRAS G12C mutation, you may be treated with the KRAS inhibitor adagrasib (Krazati) as part of a clinical trial.

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it's given and your overall health. Tell your healthcare team if you have side effects that you think are from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

Side effects of targeted therapy for pancreatic cancer include:

• fatigue
• dizziness and confusion
• skin problems, such as a rash that looks like acne on your face and neck
• nausea and vomiting
• diarrhea
• constipation
• loss of appetite
• weight gain
• low blood cell count, which can cause problems with your blood clotting, bruising more easily than normal and anemia
• liver problems
• eye and vision problems

NTRK inhibitors may cause heart problems, and KRAS inhibitors may cause kidney problems. PARP inhibitors may cause lung problems, like inflammation of the lungs, and increase your risk of developing a blood cancer like acute myeloid leukemia (AML).

Find out more about targeted therapy. To make the decisions that are right for you, ask your healthcare team questions about targeted therapy.

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.