What is Tissue-Agnostic Therapy?

Cancer therapies have often been targeted to the type of cancer being treated, like breast cancer or lung cancer. As new breakthroughs in therapy have occurred, like immunotherapy and targeted therapy, where treatments work on either the immune system or things like certain genes or proteins, respectively, some cancer treatments have become very specific, so as not to disrupt the larger body and surrounding tissues as much, and focus instead on the disease. These treatments focus on the makeup of the cancer, not just where it is in the body.

Definition of tissue-agnostic therapy

Tissue-agnostic therapy, also called tumor-agnostic therapy, is a type of treatment used to treat any type of cancer, no matter what tissue or where in the body it originated.¹ It can be used when a tumor has a specific molecular alteration/mutation or biomarker targeted by the drug or that makes it likely that the drug will work.^1,2 This means that no matter what kind of cancer it is, as long as it has a specific molecular component to it, the drug will work.

How are these drugs studied?

Typically, when a new drug is in development, clinical trials take place where patients who all have the same kind of cancer volunteer to participate in a clinical trial. This is part of how drugs become approved by the US Food and Drug Administration (FDA). Tissue-agnostic drugs are studied in clinical trials known as “basket trials.” Basket trials are clinical trials that test how a drug does in treating multiple types of cancer at the same time in the same trial.¹ This way, someone with breast cancer is in the same study as someone with brain cancer, as long as their tumors share a biomarker or alteration. This allows the researchers to see how the drug affects a wider population, instead of focusing on one cancer at a time.

Tissue-agnostic drugs used in cancer treatment

Some tissue-agnostic drugs are also drugs that have other designations, like immunotherapy drugs. Pembrolizumab (Keytruda) was the first drug to be designated as a tissue-agnostic drug, but its first FDA approval was in 2014 as a treatment for advanced or unresectable melanoma. It was subsequently approved to treat several other types of cancers, including advanced non-small cell lung cancer and refractory classical Hodgkin lymphoma.³ In May 2017, it was granted accelerated approval to treat solid tumors with a specific biomarker: microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).^1,3 This was the first cancer treatment to be approved based on a genetic marker than the location of the tumor.

Larotrectinib (Vitrakvi) was the second tissue-agnostic drug to be approved, and it treats both pediatric and adult solid-tumor cancers that have the gene fusion NTRK (neurotrophic receptor tyrosine kinase) with no known acquired resistance mutation.⁴

Entrectinib (Rozlytrek) was recently given accelerated approval in August 2019, making it the third tissue-agnostic drug used in cancer treatment. It targets adolescent and adult patients whose cancers have the NTRK gene fusion and for whom there are no effective treatments available.⁵

Every patient is unique

This new way of treating cancer means attacking the specific makeup of the tumor, not just the broad type of cancer it is. Different patients may have the same kind of general cancer, but their tumors may look very different under a microscope, depending on the biological makeup of the tumor – and it is there, in those differences, where clues to more effective treatments may lie.

If you’re interested in whether tissue-agnostic therapy might be appropriate for you, talk with your doctor about your specific kind of breast cancer and whether you’re a candidate for any kind of specific therapy. These drugs aren’t right for everyone, and even if a drug is appropriate, there are risks and benefits to any medication. Your doctor and treatment team can discuss with you what medication is best for you at this time.