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
- Other targeted therapy
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 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 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 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.
- 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
|Name of drug||Cancer stage||Indication||Biomarker||Type of agent|
|Metastatic pancreatic cancer||First-line maintenance therapy for patients whose disease has not progressed on at least 16 weeks of platinum-based chemotherapy||Inherited mutation in BRCA1 or BRCA2||PARP inhibitor|
|Tarceva (erlotinib)||Locally advanced, unresectable or metastatic pancreatic cancer||First-line therapy used in combination with gemcitabine||No biomarker required||EGFR inhibitor|
|Progressive pancreatic neuro-endocrine tumors (PNET)||Treatment of neuroendocrine tumors of pancreatic origin (PNET) that have progressed||No biomarker required||MTOR inhibitor (type of kinase inhibitor)|
|Unresectable, locally advanced or metastatic pancreatic neuro-endocrine tumors (PNET)||For treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET)||No biomarker required||Multi-target kinase inhibitor|
|Keytruda (pembrolizumab)||Metastatic or unresectable solid tumors||For treatment of solid tumors that have progressed after treatment and for which there are no other treatment options||MSI-H (Microsatellite Instability High) or MMR-D (Mismatch Repair Deficiency)||Immune checkpoint inhibitor|
|Keytruda (pembrolizumab)||Metastatic or unresectable solid tumors||
For the treatment of solid tumors that have progressed following prior treatment and for which there are no satisfactory alternative treatment options
|Tumor Mutational Burden High (TMB-H)||Immune checkpoint inhibitor|
|Vitrakvi (larotrectinib)||Metastatic solid tumors||For treatment in metastatic solid tumors where surgical resection is likely to result in severe morbidity, and for which there are no satisfactory alternative treatments or the cancer progressed following treatment||NTRK fusion||Kinase inhibitor|
The following studies may be of interest to people with pancreatic cancer and an inherited mutation.
Advanced solid tumors of any type
- NCT03565991: A Phase II Study to Evaluate the Safety and Anti-tumor Activity of Avelumab in Combination with Talazoparib in Patients with a BRCA or ATM Mutation. This study is looking at the safety and effectiveness of the combination of an immunotherapy (known as Avelumab) and a PARP inhibitor (known as Talazoparib) is for treating patients with locally advanced or metastatic solid tumors who have an inherited mutation in ATM, BRCA1 or BRCA2.
- NCT03718091: M6620 (VX-970) in Selected Solid Tumors. This is a phase 2 study looking at M6620, a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their damaged DNA. The study is specifically enrolling patients with an inherited mutation (found through genetic testing) or an acquired mutation (found through tumor testing) in BRCA1 or BRCA2, or another mutation in a gene known to affect Homologous Recombination Repair (HRR) including BARD1, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCE, FANCF, FANCM, MRE11A, NBN, PALB2, RAD51B, RAD51C, or RAD51D.
- NCT04171700: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (LODESTAR). This study is looking at the response of rucaparib in patients with various solid tumors who have an inherited mutation (found through genetic testing) or acquired mutation (found through tumor testing) in a gene known to affect Homologous Recombination Repair (HRR) including BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B.
- NCT04082572: Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers. This trial studies how well the immunotherapy agent, pembrolizumab works before surgery in treating patients with mismatch repair deficient solid cancers that have spread to nearby tissue or lymph nodes (locally advanced). This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT04001101: A Randomized Phase II Study of Anti-PD-1 and Limited Metastatic Site Radiation Therapy Versus Anti-PD-1 Alone for Patients With Microsatellite Instability-high (MSI-H) and Mismatch Repair Deficient (dMMR) Metastatic Solid Tumors. To determine if treatment is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT03607890: Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor. The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with microsatellite instability high (MSI-H) solid tumors refractory to prior PD-(L)1 therapy. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT04041310: Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors. NOUS-209-01 is a multicenter, open-label, multiple cohorts, First In Humans (FIH) clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of Nous-209 genetic polyvalent vaccine. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT03832569: Study of Pembrolizumab or Placebo Following Surgery in Patients With Microsatellite Instability High (MSI-H) Solid Tumors. This study tests the safety of the drug, pembrolizumab, and to find out how well it works to prevent cancer from coming back in people who have had a solid tumor surgically removed, but still have tumor cells in their blood. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT02715284: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors (GARNET). This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT03767348: Study of RP1 Monotherapy and RP1 in Combination With Nivolumab. RPL-001-16 is a clinical study of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT03589339: NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy. The 1100 study is an open-label, Phase I, prospective clinical study to assess the safety of intratumoral injection of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
- NCT03404960: Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy (Parpvax). This study will look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.
- NCT03375320: Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery. This study is looking at cabozantinib S-malate to see how well it works compared with placebo in treating patients with neuroendocrine tumors previously treated with everolimus that have spread to nearby tissues or lymph nodes, have spread to other places in the body, or cannot be removed by surgery.
Visit our Research Search and Enroll Tool to find additional studies.