Tumor-agnostic Drugs

For many years, drugs to treat cancer have been tested and Food and Drug Administration (FDA) approved based on where that cancer starts in the body. For example, a drug might be approved to treat breast cancer, prostate cancer, or lung cancer (or sometimes more than one type of cancer).

In recent years, much has been learned about the specific gene and protein changes in cells that drive them to grow out of control and become cancer cells. (These gene and protein changes are also called biomarkers.) Finding these specific changes in a person’s cancer cells can sometimes affect their treatment. For example, in people with lung cancer, the cancer cells are now tested for gene or protein changes to see if certain targeted therapy drugs might be helpful for them. 

Taking this a step further, some drugs are now approved based mainly on if the cancer cells have specific gene or protein changes, regardless of where the cancer started in the body. Drugs approved for use in this way are called tumor-agnostic drugs or tissue-agnostic drugs.  

Here is a list of drugs that are approved for cancer treatment based on a cancer’s protein or gene profile. A person’s cancer cells are typically tested for these changes before one of these drugs would be used.

Larotrectinib (Vitrakvi)

Some cancer cells can have changes in one of the NTRK genes, which can lead to cancer growth. Larotrectinib is a targeted drug that disables the proteins made by the abnormal NTRK genes. This drug might be an option to treat people whose cancer:

  • Has an abnormal NTRK gene AND
  • Has spread to distant parts of the body (stage 4 cancer) or cannot be removed with surgery AND
  • Has grown while on other treatments or has no other available treatment options

This drug is a pill or liquid, typically taken twice a day.

Possible side effects of larotrectinib

Common side effects include muscle and joint pain, cough, dizziness, fatigue, nausea, vomiting, constipation, fever, abdominal pain, and diarrhea.

Other side effects can include abnormal liver test results, low red and white blood cell counts, and low blood calcium levels.

Entrectinib (Rozlytrek)

Some cancer cells can have changes in one of the NTRK genes, which can lead to cancer growth. Entrectinib is a targeted drug that disables the proteins made by the abnormal NTRK genes. This drug might be an option to treat people whose cancer:

  • Has an abnormal NTRK gene AND
  • Has spread to distant parts of the body (stage 4 cancer) or cannot be removed with surgery AND
  • Has grown while on other treatments or has no other available treatment options

This drug is a pill, typically taken once a day.

Other approved uses of this drug: Entrectinib can also be used to treat people with metastatic (stage 4) non-small cell lung cancer (NSCLC) when the cancer cells have an abnormal ROS1 gene.

Possible side effects of entrectinib

Common side effects include dizziness, fatigue, cough, nausea, vomiting, constipation, weight gain, joint pain, and diarrhea.

Less common but serious side effects can include abnormal liver tests, heart problems, shortness of breath, bone fractures, and confusion.

Pembrolizumab (Keytruda)

Pembrolizumab is a type of immunotherapy drug known as an immune checkpoint inhibitor. It works on PD-1, a protein on immune cells called T cells that normally helps keep them from attacking other cells in the body (including cancer cells). By blocking PD-1, pembrolizumab boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

This drug might be an option to treat some advanced cancers, typically after other treatments have been tried or when no other good treatment options are available, if the cancer cells have any of the following:

  • A high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR)
  • A high tumor mutational burden (TMB-H), meaning the cancer cells have many gene mutations

This drug is an intravenous (IV) infusion, typically given every 3 or 6 weeks.

Other approved uses of this drug: Pembrolizumab can also be used to treat people with many other specific types of cancer, such as lung cancer and melanoma skin cancer.

Possible side effects of pembrolizumab

Common side effects include fatigue, muscle and joint pain, cough, rash, fever, nausea, abdominal (belly) pain, constipation, poor appetite, shortness of breath, low thyroid hormone levels, and diarrhea.

Infusion reactions: Some people might have an infusion reaction while getting this drug. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting a pembrolizumab infusion.

Autoimmune reactions: This drug basically removes one of the safeguards on the body’s immune system. Sometimes this causes the immune system to attack other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

It’s very important to report any new side effects to your health care team right away. If you do have a serious side effect, treatment may need to be stopped and you may be given high doses of corticosteroids to suppress your immune system.

Dostarlizumab (Jemperli)

Dostarlizumab is a type of immunotherapy drug known as an immune checkpoint inhibitor. It works on PD-1, a protein on immune cells called T cells that normally helps keep them from attacking other cells in the body (including cancer cells). By blocking PD-1, pembrolizumab boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

Dostarlizumab might be an option for people with advanced or recurrent cancer if the cancer cells have a defect in a mismatch repair gene (dMMR), typically after other treatments have been tried and when no other good treatment options are available.

This drug is given as an intravenous (IV) infusion, typically every 3 weeks at first, and then every 6 weeks.

Other approved uses of this drug: Dostarlizumab might also be used to treat advanced or recurrent endometrial cancer with a defect in a mismatch repair gene (dMMR), typically after other treatments have been tried.

Possible side effects of dostarlizumab

Common side effects include fatigue, nausea, diarrhea, and anemia. Less common but possibly serious side effects can include low blood protein levels, low sodium levels, and low white blood cell counts.

Infusion reactions: Some people might have an infusion reaction while getting this drug. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting a dostarlizumab infusion.

Autoimmune reactions: This drug basically removes one of the safeguards on the body’s immune system. Sometimes this causes the immune system to attack other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

It’s very important to report any new side effects to your health care team right away. If you do have a serious side effect, treatment may need to be stopped and you may be given high doses of corticosteroids to suppress your immune system.

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 journalists, editors, and translators with extensive experience in medical writing.

Drugs Approved for Solid Tumors Anywhere in the Body. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/drugs/solid-tumors. Updated August 26, 2021. Accessed February 14, 2022.

FDA approves pembrolizumab for adults and children with TMB-H solid tumors. U.S. Food & Drug Administration. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. Published June 17, 2020. Accessed February 14, 2022.

FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. U.S. Food & Drug Administration. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors. Published February 1, 2022. Accessed February 14, 2022.

FDA News Release: FDA approves first cancer treatment for any solid tumor with a specific genetic feature. U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cancer-treatment-any-solid-tumor-specific-genetic-feature. Published May 23, 2017. Updated March 28, 2018. Accessed February 14, 2022.

FDA News Release: FDA Approves Immunotherapy for Endometrial Cancer with Specific Biomarker. U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-immunotherapy-endometrial-cancer-specific-biomarker. Published April 22, 2021. Accessed February 14, 2022.

FDA News Release: FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor. U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-third-oncology-drug-targets-key-genetic-driver-cancer-rather-specific-type-tumor. Published August 15, 2019. Accessed February 14, 2022.

Offin M, Liu D, Drilon A. Tumor-Agnostic Drug Development. Am Soc Clin Oncol Educ Book. 2018;38:184-187. doi:10.1200/EDBK_200831.

References

Drugs Approved for Solid Tumors Anywhere in the Body. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/drugs/solid-tumors. Updated August 26, 2021. Accessed February 14, 2022.

FDA approves pembrolizumab for adults and children with TMB-H solid tumors. U.S. Food & Drug Administration. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. Published June 17, 2020. Accessed February 14, 2022.

FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. U.S. Food & Drug Administration. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors. Published February 1, 2022. Accessed February 14, 2022.

FDA News Release: FDA approves first cancer treatment for any solid tumor with a specific genetic feature. U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cancer-treatment-any-solid-tumor-specific-genetic-feature. Published May 23, 2017. Updated March 28, 2018. Accessed February 14, 2022.

FDA News Release: FDA Approves Immunotherapy for Endometrial Cancer with Specific Biomarker. U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-immunotherapy-endometrial-cancer-specific-biomarker. Published April 22, 2021. Accessed February 14, 2022.

FDA News Release: FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor. U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-third-oncology-drug-targets-key-genetic-driver-cancer-rather-specific-type-tumor. Published August 15, 2019. Accessed February 14, 2022.

Offin M, Liu D, Drilon A. Tumor-Agnostic Drug Development. Am Soc Clin Oncol Educ Book. 2018;38:184-187. doi:10.1200/EDBK_200831.

Last Revised: February 15, 2022

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