Retevmo & RET Gene Testing: Why Biomarker Results Matter?

“Your tumor tested positive for a RET (Rearranged during transfection) gene alteration.” For many people with cancer, hearing the term RET for the first time can raise questions: What does RET mean, and how could one genetic finding affect my treatment?

The answer lies in precision oncology, an approach to cancer care that uses the genetic and molecular features of a tumor to guide treatment decisions. Through biomarker testing, doctors can identify specific alterations that may be targeted with specialized therapies. One such target is the RET gene, which can be altered in certain cancers, including non-small cell lung cancer (NSCLC) and advanced medullary thyroid cancer (MTC). When a tumor carries a relevant RET alteration, a RET-directed therapy such as Retevmo (selpercatinib) may be considered. ^[1]

This is why biomarker testing is an important first step, it helps determine whether a patient may be eligible for a targeted treatment.

What Is Biomarker Testing? 

Think of a biomarker as a biological clue that can provide information about a person's cancer.

Biomarker testing looks for genes, proteins, and other substances, known as biomarkers or tumor markers, that can provide information about cancer. Because every person's cancer can have a unique pattern of biomarkers, these tests may help doctors understand how a particular tumor behaves and whether certain treatments are likely to work.

Biomarker testing for cancer treatment may also be referred to as:

 - Tumor testing

 - Tumor genetic testing

 - Genomic testing or genomic profiling

 - Molecular testing or molecular profiling

 - Somatic testing

 - Tumor subtyping

The results can help doctors and patients make more informed treatment decisions. Some cancer treatments, including targeted therapies and immunotherapies, may only work when specific biomarkers are present.

How Is Biomarker Testing Done? 

If you and your healthcare team decide that biomarker testing should be part of your cancer care, a sample of your cancer cells will be collected.

For a solid tumor, the sample may be obtained during surgery. If surgery is not being performed, your doctor may recommend a biopsy of the tumor. The collected sample is then sent to a specialized laboratory, where it is analyzed for specific biomarkers.

The laboratory report may identify biomarkers present in the cancer cells and indicate whether there are treatments that could potentially work for that particular cancer.

Biomarkers have become an important part of modern cancer care, helping with early detection, treatment response monitoring, and the development of personalized treatment strategies.

What Is the RET Gene, and Why Does It Matter?

The RET gene plays an important role in cell growth and differentiation, as well as the development of nerve cells in the body. Changes in the RET gene or abnormal activation of RET, resulting from missense variants, gene fusions, or overexpression, can cause the protein produced by this gene to become overactive. This abnormal activity may contribute to uncontrolled growth of cells, including cancer cells. ^[3,4]

RET gene mutations can cause certain genetic conditions as well as some cancers, including non-small cell lung cancer (NSCLC) and thyroid cancer. Overall, RET alterations are detected in approximately 2% of human cancers, highlighting their importance as both diagnostic biomarkers and potential therapeutic targets. ^[3,4]

How Is a RET Gene Alteration Detected?

Testing for RET gene alterations is typically performed using next-generation sequencing (NGS). NGS can detect both RET fusions and point mutations from a single tumor tissue or liquid biopsy sample.

Other techniques, although not routinely recommended, include fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and immunohistochemistry, and may be used in specific situations. However, NGS is generally preferred because of its accuracy and its ability to identify the fusion partner gene.

What Is Retevmo and How Does It Work?

Retevmo is the brand name for selpercatinib, a medicine designed to target RET, which can act as a primary driver in certain RET-driven cancers, including ^[1,5]:

 - Adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread.

 - Adults and children 12 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy).

 - Adults and children 12 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working.

 - Adults with locally advanced solid tumors (cancers) or solid tumors that have spread and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.

Retevmo works by selectively blocking the RET protein, thereby interrupting abnormal signaling that can drive tumor growth in RET fusion-positive or RET mutation-positive cancers. However, Retevmo may affect both healthy cells and tumor cells. As a result, treatment can cause side effects like dark “tea-colored” urine, bleeding or bruising, shortness of breath, confusion, headache, etc. including some that may be serious. ^[1,9]

Why Does RET Biomarker Testing Matter Before Starting Retevmo?

Retevmo (selpercatinib) is a highly selective targeted therapy for RET alteration. Testing for RET is therefore essential to identify patients who may be eligible for treatment with Retevmo. ^[1]

Clinical studies have demonstrated responses to Retevmo in patients with confirmed RET alterations. In a confirmatory analysis, it was found that nearly 1 in 2 patients (47%) responded to Retevmo, with responses lasting a median of more than two years. ^[10]

Overall response rates (ORRs) within the approved patient populations ranged from 64% in prior platinum-treated RET fusion–positive NSCLC to 100% in systemic therapy–naïve RET fusion–positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. ^[11]

These results highlight an important principle of precision oncology: the treatment is directed at a specific molecular target, so identifying that target is a crucial part of treatment selection.

Accordingly, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for RET alterations in appropriate patients with advanced and/or metastatic NSCLC and thyroid carcinoma to determine if they are eligible for RET inhibitors such as selpercatinib (Retevmo). ^[12,13]

What Can You Expect During Treatment Monitoring?

Starting a targeted treatment does not mean monitoring stops. Because Retevmo can affect healthy cells besides tumor cells, regular monitoring is an important part of treatment.

Your healthcare team may monitor several aspects of your health during treatment. Liver enzymes, including ALT and AST, are checked before starting Retevmo, every two weeks during the first three months, and monthly thereafter. Blood pressure is also monitored closely. Uncontrolled hypertension needs to be addressed before starting treatment and managed throughout therapy. Because Retevmo can prolong the QT interval on an ECG, doctors may also monitor heart rhythm, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment. Your healthcare team may also watch for signs of lung inflammation, unusual bleeding, and problems with wound healing, particularly if surgery is planned. ^[1]

Questions to Ask Before Starting Retevmo:

Learning that a genetic test may influence your treatment can understandably lead to questions. Consider discussing the following with your oncologist:

 - Has my tumor been tested for a RET fusion or RET mutation? If so, which testing method was used?

 - Is Retevmo the right treatment option for my specific cancer type and RET alteration?

 - How often will my liver function, blood pressure, and heart rhythm be monitored?

 - Which side effects should I report to my healthcare team immediately?

 - If I have had other biomarker tests previously, does this RET result change my treatment plan?

Conclusion: Let the Biomarker Lead the Way

Retevmo offers a precise, targeted option for patients whose cancers are driven by RET alterations, but its value depends entirely on knowing that alteration is actually present. RET biomarker testing is what separates patients who are likely to benefit from Retevmo from those who are not, making it an essential first step rather than an optional one. If you or a loved one has been diagnosed with NSCLC, thyroid cancer, or another solid tumor, ask your care team whether RET testing has been done. Your oncologist can guide you on testing and whether this treatment path is right for you.

Medical Disclaimer: 

This information is provided for educational purposes only and is not a substitute for professional medical advice. Medicine should only be taken under the guidance of a qualified healthcare provider. Patients should always consult their doctor for advice on diagnosis, treatment, and medication use, and should not make changes to their prescribed therapy without medical supervision.

References:

 - Eli Lilly and Company. Retevmo (selpercatinib) prescribing information. Indianapolis, IN: Eli Lilly and Company.

 - National Cancer Institute. Biomarker testing for cancer treatment. Bethesda (MD): National Cancer Institute; 2021.

 - National Cancer Institute. RET gene. NCI Dictionary of Cancer Terms. Bethesda (MD): National Cancer Institute.

 - Ricciardi Tenore C, Tulli E, Perrucci A, Bertozzi R, Fortuna L, Maneri G, Santonocito C, Urbani A, De Bonis M, Minucci A. RET Gene Alterations in Clinical Practice: A Comprehensive Review and Database Update. Genes (Basel). 2025 Dec 9;16(12):1472

 - Li T, Yang WY, Liu TT, Li Y, Liu L, Zheng X, Zhao L, Zhang F, Hu Y. Advances in the Diagnosis and Treatment of a Driving Target: RET Rearrangements in non-Small-Cell Lung Cancer (NSCLC) Especially in China. Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338221148802

 - Gregg JP, Li T, Yoneda KY. Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey. Transl Lung Cancer Res. 2019;8(3):286-301.

 - Suh JH, Johnson A, Albacker L, et al. Comprehensive genomic profiling facilitates implementation of the National Comprehensive Cancer Network Guidelines for lung cancer biomarker testing and identifies patients who may benefit from enrollment in mechanism-driven clinical trials. 2016;21(6):684-691.

 - Eli Lilly and Company. RET testing and test methods: how to test for RET [Internet]. Retevmo (selpercatinib) HCP.

 - Eli Lilly and Company. Lilly's Retevmo (selpercatinib) demonstrated an 83% reduction in the risk of disease recurrence or death as adjuvant therapy for people with early-stage RET fusion-positive lung cancer. News release. May 31, 2026

 - Gastroenterology Advisor. Retevmo earns traditional approval for RET-driven advanced solid tumors: LIBRETTO-001 response data

 - FDA approval summary: Selpercatinib for the treatment of advanced RET fusion-positive solid tumors. Clin Cancer Res. 2021;27(8):2130-2136.

 - National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Non-Small Cell Lung Cancer. Version 5.2022. Plymouth Meeting, PA: National Comprehensive Cancer Network; 2022.

 - National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Thyroid Carcinoma. Version 3.2022. Plymouth Meeting, PA: National Comprehensive Cancer Network; 2022