The importance of biomarker testing to inform treatment decisions for patients with some advanced cancers

Updated on: April 7, 2025 / 9:43 AM PDT / Sponsored Content

Sponsored by and provided by Bristol Myers Squibb

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Cancer is often caused by genetic mutations, which can lead to abnormal cell growth in the body. One type is called the KRAS G12C mutation, which happens in the KRAS protein.[1] KRAS acts as the on-off switch for cell growth.[2] When functioning normally, it tells a cell to stop growing, but when it is mutated, it can set off a domino effect that may make the cells continue to generate and develop into some of the most aggressive cancers.[2, 3] KRAS mutations are found in about one-fourth of all cancers, including lung, colorectal, and several other types of cancers [1, 4,5], and can be identified through a biomarker test, to help guide treatment discussions.[6,7,8]

The Importance of Biomarker Testing
A person's cancer may have a unique pattern of biomarkers, which can show signs of a normal or abnormal process of a condition or disease. A biomarker can also tell how well the body may respond to a treatment for a disease or condition. Biomarker testing is a way to look for genes and proteins that can provide information about the type of cancer a person has.[6,7,8]

However, some patients with the KRAS G12C mutation are not getting biomarker testing. Doctors can test for the KRAS G12C mutation by using a biopsy, either tissue from the tumor (a tissue-based test) or blood (a liquid biopsy test).[9,10,11] Colorectal cancer (CRC) with a KRAS G12C mutation occurs in approximately 1 in 30 of CRC patients [12] and has historically been challenging to treat. In non-small cell lung cancer (NSCLC), a type of lung cancer, the KRAS G12C variant is detected in about 1 in 8 patients.[13, 14] If you or your loved one has CRC or NSCLC, it is important to ask your doctor to conduct broad biomarker testing, including for KRAS mutations. Knowing the results of this test can help doctors find the best treatment approach for you.[9]

Learn About KRAZATI® (adagrasib) - A Targeted Therapy for Adults with Previously Treated KRAS G12C-Positive Advanced NSCLC or CRC
For those who are diagnosed with the KRAS G12C mutation, there may be targeted treatment options available. One FDA-approved treatment option that was intentionally designed to meet the challenge of KRAS G12C mutations is KRAZATI - an FDA-approved chemo-free, oral, targeted therapy you can take at home.[15] KRAZATI works by targeting KRAS G12C to help suppress tumor growth.[15] KRAZATI is approved to treat adults with NSCLC that has spread to other parts of the body or cannot be removed by surgery, and whose tumor has an abnormal KRAS G12C gene, and who have received at least one prior treatment for their cancer. KRAZATI is also approved in combination with cetuximab to treat adults with CRC that has spread to other parts of the body or cannot be removed by surgery, and whose tumor has an abnormal KRAS G12C gene, and who have previously received certain chemotherapy medicines.[15]

Talk to a healthcare professional to see if you or a loved one might be eligible.

KRAZATI's Efficacy and Safety Seen in Clinical Trials
KRAZATI has been evaluated in clinical trials across NSCLC and CRC to date. KRAZATI was tested in a clinical trial of 116 adults with advanced NSCLC who had received prior treatment. The trial evaluated how many patients responded to KRAZATI, meaning their tumors shrank or disappeared, as well as how long the tumor responded to the medicine.[15]

Results showed that 43% of people (43 of 112 evaluable patients) saw tumors shrink or disappear, of whom 1 person saw all signs of cancer disappear, and 47 people saw a decrease in tumor size. Of those people whose tumor responded to treatment, the duration of response was 8.5 months (median) with KRAZATI.[15] KRAZATI may cause serious side effects, including stomach and intestinal (gastrointestinal) problems, changes in the electrical activity of your heart called QTc prolongation, liver problems, and lung or breathing problems.[15]

In CRC, KRAZATI was tested in combination with cetuximab in a clinical trial of 94 adults with KRAS G12C-positive advanced CRC who previously received certain chemotherapy medicines. The trial evaluated how many people responded to KRAZATI with cetuximab and how long their tumors responded to treatment. 34% of participants saw tumors shrink (objective response rate). Based on 94 people, 32 people saw a decrease in tumor size. No person saw their tumors disappear completely. Of those people (n=32) whose tumors responded to treatment, the median duration of response was 5.8 months.[15]

The most common side effects of KRAZATI when used alone for NSCLC include nausea, diarrhea, vomiting, tiredness, muscle and bone pain, kidney problems, swelling, decreased appetite, and trouble breathing. The most common side effects when KRAZATI is used in combination with cetuximab for CRC include skin rash, nausea, diarrhea, vomiting, tiredness, muscle and bone pain, headache, dry skin, stomach pain, decreased appetite, swelling, low red blood cell count, cough, dizziness, constipation, and nerve damage in the arms and legs.

Talk to a healthcare professional to see if KRAZATI is the right treatment method for you.
To learn more, visit KRAZATI website: https://www.krazati.com/

USE AND IMPORTANT SAFETY INFORMATION

What is KRAZATI?

KRAZATI is a prescription medicine used in adults:

alone to treat non-small cell lung cancer (NSCLC)

that has spread to other parts of the body or cannot be removed by surgery, and
whose tumor has an abnormal KRAS G12C gene, and
who have received at least one prior treatment.

in combination with a medicine called cetuximab to treat colon or rectal cancer (CRC)

that has spread to other parts of the body or cannot be removed by surgery, and
whose tumor has an abnormal KRAS G12C gene, and
who have previously received certain chemotherapy medicines.

Your healthcare provider will perform a test to make sure that KRAZATI is right for you.

It is not known if KRAZATI is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Before taking KRAZATI, tell your healthcare provider about all of your medical conditions, including if you:

have any heart problems, including heart failure and congenital long QT syndrome
have liver problems
are pregnant or plan to become pregnant. It is not known if KRAZATI can harm your unborn baby
are breastfeeding or plan to breastfeed. It is not known if KRAZATI passes into your breastmilk. Do not breastfeed during treatment and for 1 week after your last dose of KRAZATI

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. KRAZATI can affect the way other medicines work, and other medicines can affect how KRAZATI works.

KRAZATI can cause serious side effects, including:

Stomach and intestinal (gastrointestinal) problems. Stomach and intestinal side effects, including nausea, diarrhea, or vomiting, are common with KRAZATI but can also sometimes be severe. KRAZATI can also cause serious stomach and intestinal side effects such as bleeding, obstruction, inflammation of the colon (colitis), and narrowing (stenosis)

Call your healthcare provider if you develop any of the signs or symptoms of stomach or intestinal problems listed above during treatment with KRAZATI
Your healthcare provider may prescribe an antidiarrheal medicine or anti-nausea medicine, or other treatment, as needed

Changes in the electrical activity of your heart called QTc prolongation. Certain changes can occur in the electrical activity of your heart during treatment with KRAZATI, and can be seen on a test called an electrocardiogram (ECG or EKG). QTc prolongation can increase your risk for irregular heartbeats that can be life-threatening, such as torsades de pointes, and can lead to sudden death

You should not take KRAZATI if you have congenital long QT syndrome or if you currently have QTc prolongation. See "Before taking KRAZATI, tell your healthcare provider about all of your medical conditions, including if you:"

Your healthcare provider should monitor the electrical activity of your heart and the levels of body salts in your blood (electrolytes) especially potassium and magnesium before starting and during treatment with KRAZATI if you have heart failure, a slow heart rate, abnormal levels of electrolytes in your blood, or if you take a medicine that can prolong the QT interval of your heartbeat
Tell your healthcare provider if you feel dizzy, lightheaded, or faint, or if you get abnormal heartbeats during treatment with KRAZATI

Liver problems. Abnormal liver blood test results are common with KRAZATI and can sometimes be severe. Your healthcare provider should do blood tests before starting and during treatment with KRAZATI to check your liver function. Tell your healthcare provider right away if you develop any signs or symptoms of liver problems, including:

your skin or white part of your eyes turns yellow (jaundice), dark or "tea-colored" urine, light-colored stools (bowel movements), tiredness or weakness, nausea or vomiting, bleeding or bruising, loss of appetite, pain, aching, or tenderness on the right side of your stomach area (abdomen)

Lung or breathing problems. KRAZATI may cause inflammation of the lungs that can lead to death. Tell your healthcare provider or get emergency medical help right away if you have new or worsening shortness of breath, cough, or fever

The most common side effects

The most common side effects of KRAZATI when used alone for NSCLC include: nausea, diarrhea, vomiting, tiredness, muscle and bone pain, kidney problems, swelling, decreased appetite, trouble breathing
The most common side effects when KRAZATI is used in combination with cetuximab for CRC include: skin rash, nausea, diarrhea, vomiting, tiredness, muscle and bone pain, headache, dry skin, stomach pain, decreased appetite, swelling, low red blood cell count, cough, dizziness, constipation, nerve damage in the arms and legs

Certain abnormal blood test results are common during treatment with KRAZATI, when used alone or in combination with cetuximab. Your healthcare provider will monitor you for abnormal blood tests and treat you if needed.

KRAZATI may cause fertility problems in males and females, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of KRAZATI. Call your doctor for medical advice about side effects. You may report side effects to the FDA. Visit fda.gov/medwatch, or call 1-800-FDA-1088. You may also report side effects to 1-844-647-2841.

Please see KRAZATI Patient Information.

References:

[1] Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal transduction and Targeted Therapy. 2021; 366. Published online November 15, 2021. https://www.nature.com/articles/s41392-021-00780-4. Accessed July 24, 2024.

[2] Ledford H. Cancer: the Ras renaissance. Nature. 2015;520(7547):278-280.

[3] Ostrem JM, Shokat KM. Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design. Nat Rev Drug Discov. 2016;15(11):771-785.

[4] American Cancer Society. Cancer Facts & Figures 2024. Accessed July 3, 2024.

[5] O'Sullivan É, Keogh A, Henderson B, et al. Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer. Cancers. 2023;15(6):1635. doi:10.3390/cancers15061635

[6] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.3.2024. Accessed May 24, 2024.

[7] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.2.2024. Accessed April 30, 2024.

[8] Kerr K, Bibeau F, Thunnissen E , et al. The evolving landscape of biomarker testing for non-small cell lung cancer in Europe, Lung Cancer, Vol 154, 2021, Pages 161-175, ISSN 0169-5002, https://doi.org/10.1016/j.lungcan.2021.02.026.

[9] Biomarker testing for cancer treatment. National Cancer Institute. Updated December 14, 2021. Accessed August 24, 2022.

[10] Nacchio M, Sgariglia R, Gristina V, et al. KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting. J Thorac Dis. 2020;12(7):3836-3843. doi:10.21037/jtd.2020.01.19

[11] Mauri, G., Vitiello, P.P., Sogari, A. et al. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer. Br J Cancer 127, 394–407 (2022). https://doi.org/10.1038/s41416-022-01769-8

[12] Yaeger R, Weiss J, Pelster MS, et al. Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C. N Engl J Med. 2023;388(1):44-54. doi: 10.1056/nejmoa2212419.

[13] Campbell JD, Alexandrov A, Kim J, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nature Genetics. 2016;48:607-616.

[14] Nassar A, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type. N Engl J Med. 2021;384:185-187. doi: 10.1056/nejmc2030638.

[15] KRAZATI®. Prescribing information. Princeton, NJ. Mirati Therapeutics, Inc., a Bristol Myers Squibb Company; 2024.

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