Selpercatinib

Introduction: What is Selpercatinib?

Selpercatinib is a targeted therapy medication primarily used in the treatment of certain types of cancer. Specifically, it is designed to inhibit the activity of the RET (rearranged during transfection) protein, which can become abnormally activated in various cancers. By blocking this protein, Selpercatinib helps to slow down or stop the growth of cancer cells that rely on RET for their proliferation. It is particularly effective in treating locally advanced or metastatic non-small cell lung cancer (NSCLC), advanced or metastatic medullary thyroid cancer (MTC), as well as other RET fusion-positive solid tumors that harbor specific RET gene alterations.

Uses of Selpercatinib

Selpercatinib has been approved for several medical uses, including:

• Non-Small Cell Lung Cancer (NSCLC): It is indicated for adults with metastatic NSCLC who have a RET fusion, a specific genetic alteration.
• Medullary Thyroid Cancer (MTC): Selpercatinib is also approved for adults and pediatric patients aged 12 years and older with advanced or metastatic MTC that is RET positive.
• RET Fusion-Positive Thyroid Cancer and Other Solid Tumors: Approved for adult and pediatric patients 2 years and older with advanced or metastatic RET fusion-positive thyroid cancer (radioactive iodine-refractory if appropriate) and other locally advanced or metastatic solid tumors that have progressed on prior therapy.

How Does It Work?

Selpercatinib works by specifically targeting and inhibiting the RET protein, which is involved in cell signaling pathways that promote cell growth and division. In cancers where RET is mutated or overactive, this signaling can lead to uncontrolled cell proliferation. By blocking RET, Selpercatinib disrupts these signals, effectively slowing down or stopping the growth of cancer cells. This targeted approach helps to minimize damage to normal cells, which is a significant advantage over traditional chemotherapy.

Dosage and Administration

Selpercatinib is administered orally in the form of a tablet. The recommended dosage for adults and adolescents ?12 years is 160 mg orally twice daily if body weight ?50 kg, or 120 mg orally twice daily if <50 kg, with or without food. It is essential to take Selpercatinib at the same time each day to maintain consistent levels of the medication in the body. Patients should swallow the tablets whole and can take them with or without food.

Side Effects of Selpercatinib

Like all medications, Selpercatinib can cause side effects.

Common side effects include:

• Fatigue
• Diarrhea
• Nausea
• Vomiting
• Constipation
• Abdominal pain
• Increased liver enzymes
• Dry mouth
• Edema
• Rash

Serious side effects may include:

• Hepatotoxicity (liver damage)
• Hypertension (high blood pressure)
• QT prolongation (a heart rhythm condition)
• Severe allergic reactions
• Interstitial lung disease/pneumonitis
• Hemorrhage
• Impaired wound healing

Patients should report any unusual symptoms or severe side effects to their healthcare provider immediately.

Drug Interactions

Selpercatinib can interact with several medications, which may affect how it works or increases the risk of side effects. Major drug interactions include:

• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) can increase Selpercatinib levels in the blood.
• Strong CYP3A4 inducers (e.g., rifampin, St. John?s Wort) can decrease its effectiveness.
• Other medications that affect liver enzymes may also alter Selpercatinib's metabolism.
• Combined P-gp and strong CYP3A inhibitors (e.g., itraconazole) require RETEVMO dose reduction; avoid strong CYP2C8 inhibitors/inducers.

Patients should inform their healthcare provider of all medications, supplements, and herbal products they are taking.

Benefits of Selpercatinib

The use of Selpercatinib offers several clinical advantages:

• Targeted Therapy: It specifically targets RET alterations, leading to potentially better outcomes with fewer side effects compared to traditional chemotherapy.
• Oral Administration: Being an oral medication, it provides convenience and ease of use for patients.
• Clinical Efficacy: Clinical trials have shown promising results in terms of tumor response rates and progression free survival in patients with RET altered cancers.
• Quality of Life: Many patients report an improved quality of life while on Selpercatinib compared to other treatment options.

Contraindications of Selpercatinib

Patients with a known hypersensitivity to Selpercatinib or any of its components should avoid using Selpercatinib.

Precautions and Warnings

Before starting Selpercatinib, patients should undergo specific lab tests to assess liver function, as liver toxicity is a potential risk. Regular monitoring of blood pressure is also recommended, as hypertension can occur. Patients should discuss their complete medical history with their healthcare provider, including any history of heart problems or liver disease. Advise embryo-fetal toxicity (can cause fetal harm; use effective contraception during treatment and for 1 week after); monitor for interstitial lung disease (withhold if suspected).

FAQs

• What is Selpercatinib used for? Selpercatinib is used to treat certain types of cancer, including non-small cell lung cancer and medullary thyroid cancer that have RET gene alterations.
• How is Selpercatinib taken? It is taken orally in tablet or capsule form, 160 mg twice daily (or weight-based for pediatrics), with or without food.
• What are the common side effects? Common side effects include fatigue, diarrhea, nausea, and increased liver enzymes.
• Can Selpercatinib be taken with other medications? Some medications can interact with Selpercatinib. Always inform your doctor about all the medications you are taking.
• Is Selpercatinib safe during pregnancy? No, Selpercatinib is not recommended during pregnancy due to potential harm to the fetus.
• How does Selpercatinib work? It inhibits the RET protein, which is involved in cancer cell growth, thereby slowing down or stopping tumor growth.
• What should I do if I miss a dose? If it is close to the next dose (within 6 hours), skip the missed dose and continue with your regular schedule. Do not take two doses at once.
• Are there any serious side effects? Yes, it is approved for pediatric patients 2 years and older with RET-mutant medullary thyroid cancer.
• Can children take Selpercatinib? Yes, it is approved for pediatric patients aged 12 years and older with RET positive medullary thyroid cancer.
• How long will I need to take Selpercatinib? The duration of treatment varies based on individual response and the specific cancer being treated. Your doctor will provide guidance.

Brand Names

Selpercatinib is marketed under the brand name Retevmo.

Conclusion

Selpercatinib represents a significant advancement in the treatment of RET altered cancers, offering targeted therapy with a favorable side effect profile. Its ability to specifically inhibit the RET protein makes it a valuable option for patients with non-small cell lung cancer and medullary thyroid cancer. As with any medication, it is essential for patients to discuss their treatment options with their healthcare provider to determine the best course of action.