Drug Overview

Selpercatinib is a modern, highly specific medication used to treat certain types of cancer that are caused by a change in a specific gene. It belongs to a group of advanced medicines that target the root cause of tumor growth at the cellular level. Because it is designed to find and attach only to specific markers on cancer cells, it is a key example of precision medicine.

This medication is taken as a capsule by mouth. It is primarily used for patients whose cancer has spread to other parts of the body or cannot be removed by surgery, and who have a specific genetic “rearrangement” or “mutation” known as RET.

• Generic name: Selpercatinib
• US Brand names: Retevmo
• Drug Class: Kinase Inhibitor, RET Receptor Tyrosine Kinase Inhibitor
• Route of Administration: Oral (Capsules)
• FDA Approval Status: FDA Approved

What Is It and How Does It Work? (Mechanism of Action)

Selpercatinib is a Targeted Therapy and a Smart Drug. Unlike traditional chemotherapy, which attacks all fast-growing cells in the body, selpercatinib is engineered to seek out and turn off a specific “on-switch” found in certain cancer cells.

At the molecular level, this drug works by blocking a protein called RET (Rearranged during Transformation). In a healthy body, the RET protein acts like a receiver on the outside of cells, waiting for signals to tell the cell to grow or move. However, in some cancers, the RET gene becomes broken or fused with another gene. This broken gene creates a RET protein that is permanently stuck in the “on” position.

When the RET protein is always “on,” it sends constant, rapid signals deep into the cell through communication pathways like the MAPK and PI3K pathways. These signals tell the cancer cell to multiply out of control and resist dying. Selpercatinib binds directly to the RET protein and blocks its activity. By physically plugging this “on-switch,” the drug stops the growth signals from reaching the rest of the cell. This causes the tumor to stop growing and often leads to the death of the cancer cells.

FDA-Approved Clinical Indications

Selpercatinib is approved for use in specific adult and pediatric patients (12 years and older) whose tumors have been confirmed to have a RET gene alteration by a laboratory test.

Oncological uses

• Metastatic RET fusion-positive non-small cell lung cancer (NSCLC).
• Advanced or metastatic RET-mutant medullary thyroid cancer (MTC) that requires systemic therapy.
• Advanced or metastatic RET fusion-positive thyroid cancer in patients who have received radioactive iodine and it did not work or is no longer working.
• Locally advanced or metastatic RET fusion-positive solid tumors in patients whose cancer has progressed after other treatments or who have no other satisfactory treatment options.

Non-oncological

• None at this time.

Dosage and Administration Protocols

The dose of selpercatinib is based on the patient’s body weight. It is taken twice a day, approximately every 12 hours.

Dose Adjustments

For patients with severe hepatic (liver) insufficiency, the starting dose should be reduced. If a patient is taking 160 milligrams twice daily, the dose is typically reduced to 80 milligrams twice daily. If the patient is taking 120 milligrams twice daily, it is reduced to 40 milligrams twice daily. No specific dose adjustment is required for patients with renal (kidney) insufficiency, though they should be monitored closely.

Clinical Efficacy and Research Results

Clinical data from 2020 to 2025 have shown that selpercatinib is highly effective at shrinking tumors and extending life for patients with RET-driven cancers.

In the LIBRETTO-001 clinical trial, which followed hundreds of patients, those with RET fusion-positive lung cancer who had never been treated before showed an overall response rate of 84 percent. For patients who had already received chemotherapy, the response rate was 64 percent. The duration of this response was often more than 17 months, meaning the drug kept the cancer under control for a long time.

In the LIBRETTO-531 Phase 3 trial (results reported in 2023-2024), selpercatinib was compared to standard treatments for medullary thyroid cancer. The numerical data showed that selpercatinib significantly improved progression-free survival. Patients taking selpercatinib had an 80 percent lower risk of their disease getting worse or death compared to those taking older targeted therapies like cabozantinib or vandetanib.

Safety Profile and Side Effects

While selpercatinib is targeted, it can still affect healthy tissues that use similar signaling pathways.

Black Box Warning

There is no official FDA Black Box Warning for selpercatinib.

Common side effects

These side effects are seen in greater than 10 percent of patients:

• Swelling of the hands, ankles, or feet (edema)
• High blood pressure (hypertension)
• Feeling very tired (fatigue)
• Dry mouth
• Diarrhea or constipation
• Increased liver enzymes (indicating liver stress)
• Low white blood cell counts

Serious adverse events

• Severe liver damage (hepatotoxicity)
• Severe high blood pressure that can lead to a heart attack or stroke
• Lung inflammation (interstitial lung disease/pneumonitis)
• Changes in heart rhythm (QT interval prolongation)
• Severe bleeding (hemorrhage)
• Slowed wound healing

Management strategies

High blood pressure is very common and must be managed with standard blood pressure medications. If liver enzymes rise to dangerous levels, the doctor will pause the medication until the liver recovers and then restart it at a lower dose. If a patient develops a new or worsening cough or shortness of breath, they must be checked for lung inflammation immediately.

Research Areas

Researchers are currently looking into how selpercatinib can be used earlier in the treatment process, before other chemotherapies are tried. There is also active research on using this drug in combination with immunotherapies to see if it can help the immune system recognize and attack RET-driven tumors more effectively. While not currently used in stem cell transplants, the study of how cancer stem cells develop resistance to selpercatinib is a major focus of regenerative medicine research to help prevent the cancer from returning.

Patient Management and Practical Recommendations

Pre-treatment tests to be performed

• Genetic testing (NGS) to confirm the presence of a RET gene mutation or fusion.
• Blood pressure check.
• Liver function tests (ALT, AST, and Bilirubin).
• An electrocardiogram (ECG) to check the heart’s electrical rhythm.
• Kidney function tests.

Precautions during treatment

Patients must monitor their blood pressure at home. Because the drug can affect the heart’s rhythm, certain other medications (like some antidepressants or antibiotics) should be avoided. Patients should also stop taking the drug at least 7 days before any scheduled surgery to ensure proper healing.

Do’s and Don’ts list

• Do take your doses at the same time every day to keep the drug levels steady.
• Do tell your doctor about all other medicines you take, including heart and stomach medicines.
• Do call your care team immediately if you feel your heart racing or feel dizzy.
• Don’t take an antacid (like Tums or Pepcid) at the same time as this drug; if you need them, follow your doctor’s specific timing instructions.
• Don’t eat grapefruit or drink grapefruit juice, as it can increase the levels of the drug in your body to dangerous levels.
• Don’t ignore signs of liver trouble, such as yellowing of the skin or dark urine.

Legal Disclaimer

The information provided in this guide is for educational and informational purposes only and does not constitute medical advice. Selpercatinib (Retevmo) is a prescription medication used under the strict supervision of trained medical professionals and oncologists. Always consult with a qualified healthcare professional before starting any new treatment, changing your medication regimen, or if you have questions regarding your specific medical condition or cancer treatment plan.