Author: Brittney Nichols, MPH, BSN-RN, Senior Specialist, Science & Research, GO2 for Lung Cancer

Biomarker testing is an important part of the cancer diagnosis and care continuum. For almost all people diagnosed with non-small cell lung cancer (NSCLC) biomarker testing is considered a routine part of guideline-concordant care (the minimal treatment patients should receive according to the National Comprehensive Cancer Network). However, guideline-concordant care and real-world care do not always align. At GO2, we work tirelessly to ensure all patients have access to comprehensive biomarker testing and precision medicine whenever possible.

Biomarker testing: what and when

Biomarker testing is used to look for genetic changes and driver mutations that can occur in the DNA of cells and lead to cancer development. If biomarker testing determines someone has a genetic change or mutation (such as EGFR, KRAS, or ALK), they may be able to receive targeted therapy. With the rapid development of new targeted therapies for lung cancer, it’s more important than ever that anyone with NSCLC receives biomarker testing, both at diagnosis and upon disease progression, so they receive the most effective treatment for their disease at each step of their cancer experience.

Biomarker testing when a person is first diagnosed helps the provider decide if they can start on a precision therapy, like targeted therapy. This limits their exposure to unnecessary, less specific drugs with harsher side effects.

Biomarker testing may also be used to determine if someone with NSCLC has started to resist treatment or if the cancer has begun to grow again, either at the existing tumor site or new growth. If new growth or progression has been detected, biomarker testing can help look for new mutations that may have allowed the cancer to resist or evade the current treatment (these are known as ‘resistance mutations’).

Resistance mutations have different causes. An example of a well-understood resistance mutation is the EGFR-C797S mutation that may arise in response to earlier treatment with newer third-generation EGFR-T790M targeted therapies, such as Osimetrinib (Tagrisso). The causes of other resistance mutations remain unknown. These resistance mutations may develop in response to targeted therapies or other environmental or biological factors in ways that remain unclear. The presence or development of these ‘co-mutations’ can sometimes have a profound impact on how a person responds to their treatment and how their cancer proliferates.

What are co-mutations and why do they matter?

Simply put, co-mutations are the presence of multiple genetic alternations or mutations in a person’s cancer. Co-mutations are quite common in cancer, as cancer is commonly a heterogeneous disease (meaning the tumor is made of several subpopulations of cells with different mutations, rather than all cells being the same). While not all mutations are actionable driver mutations that can be treated with an FDA-approved targeted therapy, some can still impact a person’s response to certain medications or how/where their cancer may spread. Biomarker testing at both diagnosis and progression can help clinicians better place patients on the appropriate therapy.

An example of progression and co-mutation for EGFR and cMET: A person diagnosed with EGFR-positive NSCLC starts a targeted therapy for their EGFR mutation. After 12 months of stable disease, their healthcare team finds a new lesion, biopsies it, and the results show it’s positive for both EGFR and cMET. The patient may then start a new medication (like a MET-targeted therapy or a bi-specific drug targeting both EGFR and MET) in addition to their current medication targeting the EGFR mutation.

This is just one example of a type of co-mutation and how it may impact the choice of treatment pathway. There are many different mutations out there, each with their own recommended treatments based on a person’s specific situation.

Exceptions to every rule

There are some situations where a clinician may advise that biomarker testing is not needed. These cases are uncommon, but some situations where this may happen include:

  • A person is diagnosed with NSCLC at a very early stage, and the cancer is removed locally with clean margins before it has had a chance to spread.
  • A person is diagnosed with small cell lung cancer (SCLC). While there is a lot of promising research on potential biomarkers for the diagnosis and treatment of SCLC, it is still in the early phases and has not led to any changes in the recommended practice.
  • A person doesn’t have enough tumor tissue to sample, or their tumor tissue is in a location that is difficult to biopsy. Blood-based biomarker testing is also available and can be especially helpful such cases.

If you are a person with NSCLC and your physician has not recommended or has advised against biomarker testing, some questions to consider asking them are:

  • Why do I not need biomarker testing now?
  • When may I need biomarker testing in the future?
  • What impact will this/could this have on my treatment?

Learn more and get tested

If you are a person living with or caring for someone with NSCLC and would like to learn more about biomarker testing or precision medicine, explore our free educational materials. If you’re interested in learning more, contact clinicaltrials@go2.org.