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As researchers have learned more about the changes in pancreatic cancer cells that help them grow, they have developed newer drugs to specifically target these changes. These targeted drugs work differently from standard chemo drugs. Sometimes they work when standard chemo drugs don’t, and they often have different side effects. (See What’s New in Pancreatic Cancer Research? for more information.)
A small number of pancreatic cancers have changes in the BRAF gene, specifically the BRAFV600E mutation. This gene change can lead to abnormal cell growth and cancer.
Dabrafenib (Tafinlar) and trametinib (Mekinist) are given in combination, and are treatment options for people with unresectable pancreatic cancer, if it is found to have the BRAFV600E mutation.
These drugs are taken as pills twice daily.
Common side effects of these drugs include chills, fever, night sweats, tiredness, skin rash, nausea, vomiting, diarrhea, abdominal pain, swelling of hands or feet, joint aches, decreased appetite, muscle aches and headache.
A small number of pancreatic cancers have changes in the NTRK gene. These gene changes can sometimes lead to abnormal cell growth and cancer.
Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are given as a single agent (alone) and are treatment options for people with unresectable pancreatic cancer, if it is found to have the NTRK gene fusion mutation. These drugs are taken as pills, once or twice daily.
Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea. Less common but more serious side effects can include abnormal liver tests, heart problems, and confusion.
A small number of pancreatic cancers have changes in the RET gene. These gene changes can sometimes lead to abnormal cell growth and cancer.
Selpercatinib (Retevmo) is a treatment option for people with unresectable pancreatic cancer, if it is found to have the RET gene fusion mutation.
This drug is taken as a capsule, twice daily.
Common side effects of this drug can include abnormal LFT (liver function test) values, low white blood cells and platelets, dry mouth, diarrhea, constipation, high blood pressure, tiredness, and skin rash.
A small number of pancreatic cancers have changes in the KRAS gene, specifically the KRAS G12C mutation. This gene change can lead to abnormal cell growth and cancer.
Adagrasib (Krazati) and sotorasib (Lumakras) are given as a single agent (alone) and are treatment options for people with unresectable pancreatic cancer, if it is found to have the KRAS G12C mutation. These drugs are usually considered only after the pancreatic cancer has not responded well or worsened after receiving another type of treatment.
These drugs are taken as pills, once or twice daily.
Common side effects of these drugs include nausea, decreased appetite, vomiting, diarrhea, muscle aches, and changes in liver and kidney test values. Less common but more serious side effects can include changes in laboratory values, including LFTs (liver function tests), white blood cells, red blood cells, and electrolytes (sodium and potassium).
Erlotinib (Tarceva) is a drug that targets a protein on cancer cells called EGFR, which normally helps the cells grow. In people with advanced pancreatic cancer, this drug can be given along with the chemo drug gemcitabine. Some people may benefit more from this combination than others.
This drug is taken as a pill, once a day.
Common side effects of erlotinib include an acne-like rash on the face and neck, diarrhea, loss of appetite, and fatigue. Less common but more serious side effects can include serious lung, liver, or kidney damage; holes (perforations) forming in the stomach or intestines; serious skin conditions; and bleeding or blood clotting problems.
In a small number of pancreatic cancers, the cells have changes in one of the BRCA genes (BRCA1 or BRCA2). Changes in one of these genes can sometimes lead to cancer.
Olaparib (Lynparza) is a type of drug known as a PARP inhibitor. PARP enzymes are normally involved in a pathway that helps repair damaged DNA inside cells. The BRCA genes are normally involved in a different pathway of DNA repair, and mutations in one of these genes can block that pathway. By blocking the PARP pathway as well, this drug makes it very hard for tumor cells with a mutated BRCA gene to repair damaged DNA, which often leads to their death.
Olaparib is a treatment option for people with unresectable pancreatic cancer with a germline BRCA1 or BRCA2 mutation. It is given as a maintenance therapy, specifically if the pancreatic cancer has not gotten worse after at least 4 months of platinum-based chemo (such as oxaliplatin or cisplatin).
This drug has been shown to help shrink or slow the growth of some advanced pancreatic cancers, although so far it’s not clear if it can help people live longer.
This drug is taken by mouth as pills, typically twice a day.
Common side effects of this drug can include nausea, vomiting, diarrhea or constipation, fatigue, feeling dizzy, loss of appetite, taste changes, low red blood cell counts (anemia), low white blood cell counts (with an increased risk of infection), belly pain, and muscle and joint pain. Less common but more serious side effects can include inflammation in the lungs and the development of certain blood cancers, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.
The American Cancer Society medical and editorial content team
Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.
Bekaii-Saab TS, Yaeger R, Spira AI, Pelster MS, Sabari JK, Hafez N, Barve M, Velastegui K, Yan X, Shetty A, Der-Torossian H, Pant S. Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation. J Clin Oncol. 2023 Sep 1;41(25):4097-4106. doi: 10.1200/JCO.23.00434. Epub 2023 Apr 26. PMID: 37099736.
Bhamidipati D, Yedururi S, Huse J, Chinapuvvula SV, Wu J, Subbiah V. Exceptional Responses to Selpercatinib in RET Fusion-Driven Metastatic Pancreatic Cancer. JCO Precis Oncol. 2023 Sep;7:e2300252. doi: 10.1200/PO.23.00252. PMID: 38039431.
Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. doi: 10.1056/NEJMoa1903387. Epub 2019 Jun 2. PMID: 31157963; PMCID: PMC6810605.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma. V.1.2024. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf on Feb 5, 2024.
Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21. PMID: 36546651; PMCID: PMC10506456.
Subbiah V, Kreitman RJ, Wainberg ZA, Gazzah A, Lassen U, Stein A, Wen PY, Dietrich S, de Jonge MJA, Blay JY, Italiano A, Yonemori K, Cho DC, de Vos FYFL, Moreau P, Fernandez EE, Schellens JHM, Zielinski CC, Redhu S, Boran A, Passos VQ, Ilankumaran P, Bang YJ. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med. 2023 May;29(5):1103-1112. doi: 10.1038/s41591-023-02321-8. Epub 2023 Apr 14. PMID: 37059834; PMCID: PMC10202803.
Last Revised: February 5, 2024
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