Sotorasib: A Ray of Hope for Non-small Cell Lung Cancer Patients

Overview

A cancer-fighting drug called Sotorasib is used to treat non-small-cell lung cancer. It specifically targets the G12C (glycine-to-cysteine substitution at codon 12) mutation in the protein K-Ras, which is produced by the KRAS (Kirsten rat sarcoma viral oncogene homolog) gene and is the cause of several types of cancer. Sotorasib inhibits the RAS GTPase family. The most typical adverse effects are coughing, nausea, exhaustion, diarrhea, musculoskeletal discomfort, and liver damage.

For tumors with any KRAS mutation, which makes up around 25 percent of mutations in non-small cell lung cancers, Sotorasib is the first authorized targeted treatment. Around 13 percent of individuals with non-small cell lung tumors had KRAS G12C mutations. The United States and the European Union granted Sotorasib medicinal use approvals in May 2021 and January 2022, respectively. It is regarded as a first-in-class drug by the US Food and Drug Administration.

How Does Sotorasib Work?

A particular mutant variant of the KRAS protein, frequently present in several forms of cancer, is the target of the small molecule inhibitor Sotorasib (also known as AMG 510). A GTPase protein called KRAS is essential for cell signaling pathways that control cell growth and division. Overactive KRAS proteins can result from mutations in the KRAS gene, which can help cancer develop and spread.

Once it binds to the altered KRAS protein, Sotorasib begins to operate by precisely targeting the amino acid alteration known as KRAS G12C. Due to this interaction, the protein undergoes a conformational change, which hinders downstream signaling pathways that support the survival and proliferation of cancer cells.

The U.S. Food and Drug Administration (FDA) has authorized Sotorasib to treat adult patients with locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC) who have had at least one previous systemic therapy. It is the first targeted treatment to show clinical efficacy in NSCLC patients with the KRAS G12C mutation.

Dose and Dosage of Sotorasib

AMG510, commonly known as Sotorasib, is a medication used to treat non-small cell lung cancer that carries the KRAS G12C mutation.

1. Oral tablets containing 120 milligrams (mg) and 180 mg are the only available dosage forms for Sotorasib.

2. Eight 120 mg pills or five 180 mg tablets taken orally once per day with or without meals make up the recommended daily dosage of Sotorasib, which is 960 mg.

It is crucial to take the prescription every day without crushing or chewing the tablets.

Directions

The following are basic guidelines for utilizing Sotorasib:

Tablets of Sotorasib are available and should be taken once a day, with or without meals.

1. Sotorasib should be used once a day orally in doses of 960 mg (eight 120 mg pills or five 180 mg tablets).

2. The pills must not be chewed, crushed, or broken.

3. Take the missed dosage as soon as it is recalled. Skip the missed dosage and follow the usual dosing plan if it is less than six hours before the next scheduled dose.

4. If an overdose of Sotorasib occurs, call the doctor or get help immediately.

5. Sotorasib should be kept at room temperature, away from heat sources, moisture, and direct sunlight.

Warnings

1. Sotorasib can potentially cause interstitial lung disease (ILD), a dangerous and potentially deadly lung ailment. Get immediate medical assistance if any new or worsening respiratory symptoms develop, such as coughing, breathing problems, or chest discomfort.

2. Sotorisib can potentially damage the liver and result in abnormal liver function tests. See the doctor immediately if a person suffers symptoms, including yellowing skin or eyes, stomach discomfort, or black urine.

3. Sotorasib may result in alterations in eyesight or eye discomfort, among other eye issues.

4. Other medications, including over-the-counter, prescription, and herbal supplements, may interact with Sotorasib. Consult with the doctor before using any new medications or supplements.

5. If used during pregnancy, Sotorasib may be dangerous to the unborn child. Sotorasib should not be used by women who are pregnant or trying to get pregnant. Effective birth control should be utilized throughout therapy and for one week following the final dosage of Sotorasib.

6. Since it can enter breast milk, Sotorasib poses a risk to breastfeeding infants. Sotorasib should not be taken by nursing mothers, or they should think about discontinuing it while taking the medicine.

For Patients:

What Is Non-small Cell Lung Cancer?

Non-small cell lung cancer (NSCLC) is a kind of lung cancer that develops from cells lining the airways of the lung. It makes up around 85 percent of all occurrences of lung cancer, making it the most prevalent. Small cell lung cancer (SCLC), a more aggressive kind with a propensity to spread quickly, is distinct from non-small cell lung cancer (NSCLC).

Adenocarcinoma, squamous cell carcinoma, and big cell carcinoma are the three subtypes of NSCLC that may be further classified according to the affected cells. Depending on the stage and features of the cancer, treatment options for NSCLC may include surgery, chemotherapy, radiation therapy, targeted therapy, or a combination of these modalities.

Learn More About Sotorasib

Things to Inform Doctor Before Starting Sotorasib

1. If a person has an allergy to Sotorasib, other drugs, or any of the substances in Sotorasib tablets, inform the doctor and pharmacist immediately. Get a list of the components from the chemist.

2. Inform the doctor about any other prescription and over-the-counter drugs, vitamins, dietary supplements, and herbal items they are taking or intend to use.

3. Sotorasib may interact with the following over-the-counter medicines or herbal supplements: Ranitidine, Cimetidine, Esomeprazole, Famotidine, Lansoprazole, and Omeprazole. When using Sotorasib, inform the doctor about taking these drugs. When using Sotorasib, avoid starting any drugs without first seeing the doctor.

4. Take Sotorasib either four hours before or ten hours after taking an antacid if a person is taking both.

5. Inform the doctor if one has or has previously had lung or breathing issues other than lung cancer or liver illness.

6. If pregnant or intend to become pregnant, inform the doctor right away.

7. If nursing or intend to do so, let the doctor know. While using Sotorasib and for one week following the final dosage, one shouldn't breastfeed.

When and Why to Use Sotorasib?

1. Sotorasib, often called AMG 510, is a targeted therapy medication intended to treat non-small cell lung cancer (NSCLC) that carries the G12C mutation, a particular variation in the KRAS gene.

2. Around 13 percent of NSCLC patients have the KRAS G12C mutation, which is linked to a poor prognosis and resistance to conventional therapies. To stop the mutant KRAS protein from transmitting signals that promote unchecked cell growth and division, Sotorasib binds directly to this protein.

3. After showing a significant therapeutic benefit in phase I and II clinical trials, Sotorasib was given FDA (Food and Drug Administration) approval in May 2021 for treating advanced NSCLC with the KRAS G12C mutation.

How Effective Is Sotorasib?

1. In clinical studies, Sotorasib has demonstrated promise in treating non-small cell lung cancer (NSCLC) with the KRAS G12C mutation. In patients with advanced NSCLC with the KRAS G12C mutation who had had at least one prior line of treatment, Sotorasib showed an overall response rate (ORR) of 37.1 percent. The typical response time was ten months.

2. Moreover, Sotorasib had a controllable safety profile and was well-tolerated by patients. In clinical studies, diarrhea, exhaustion, nausea, musculoskeletal discomfort, and cough were the most frequently reported adverse effects.

3. The effectiveness of Sotorasib may vary based on the particular features of each patient, including the amount and location of cancer, the existence of other medical disorders, and the patient's general health state.

Side Effects of Sotorasib

1. Diarrhea.

2. Vomiting.

3. Nausea.

4. Constipation.

5. Reduced appetite.

6. Fatigue.

7. Discomfort in the muscle or bone.

8. Stomach ache.

9. Arthritic rash.

Certain adverse effects can be quite harmful. If any of these symptoms are encountered, seek emergency care:

1. Black urine, yellowing of the skin or eyes, easier bruising or bleeding, loss of appetite, low energy, or pain on the right side of the stomach region

2. Breathing difficulty, coughing, or fever

Other side effects of Sotorasib are possible. Contact the doctor immediately if one experiences any unusual issues while taking this medication.

How to Take Sotorasib?

1. Take Sotorasib exactly as prescribed by the healthcare provider. Wait to change the dose or stop taking Sotorasib after consulting the healthcare provider.

2. Sotorasib is taken orally, usually once a day. The recommended dose is 960 mg, taken with or without food.

3. Swallow the Sotorasib tablet whole with a glass of water.

4. If the dose of Sotorasib is missed, take it as soon as remembered. However, if it is less than six hours before the next scheduled dose, skip the missed dose and resume the regular dosing schedule. Refrain from taking extra doses to make up for a missed dose.

5. If one experiences any side effects or concerns about using Sotorasib, talk to the healthcare provider as soon as possible.

6. The healthcare provider will monitor the response to Sotorasib and adjust the dose or treatment schedule as needed. Be sure to keep all the appointments with the healthcare provider.

7. Store Sotorasib tablets at room temperature, away from heat and moisture.

Missed Dose

Take the missed dosage as soon as it is recalled. Skip the missed dosage and follow the usual dosing plan if it is less than six hours before the next scheduled dose. If unintentionally take too much Sotorasib, call the doctor or get help immediately.

What Should Be Done to Treat a Sotorasib Overdose?

Sotorasib side effects such as diarrhea, lethargy, nausea, musculoskeletal discomfort, and cough are more likely to occur in an overdose.

The following actions might be taken by medical personnel, depending on the severity of the overdose:

1. Activated Charcoal: Itmay be used if the overdose was recent to assist the stomach and intestines in absorbing the extra Sotorasib.

2. Supporting Treatment: Depending on the severity of the overdose, medical personnel may offer supportive care, including keeping an eye on vital signs, giving oxygen, and giving IV fluids.

3. Sotorasib Discontinuation: Until the overdose symptoms subside, medical practitioners may discontinue prescribing Sotorasib.

4. Treatment for Symptoms: If required, medical experts may administer therapy for symptoms of an overdose, such as painkillers for musculoskeletal pain or nausea medications.

How to Maintain Sotorasib?

Sotorasib should be kept between 68°F and 77°F (20°C and 25°C) in a dry environment.

Torasib should be stored according to the following advice:

1. Keep it in its original container until it is time to take the drug.

2. Keep Sotorasib away from heat, moisture, and direct sunlight.

3. Keep children and pets away from the drug.

4. Never freeze Sotorasib.

5. Dispose of any unused or expired medicine in accordance with local legislation.

6. Before using Sotorasib, it is crucial to constantly verify the expiration date and not do so if it has passed.

For Doctors:

Indications

Sotorasib is used to treat non-small cell lung cancer (NSCLC) that carries the KRAS G12C genetic mutation. It inhibits the function of the protein KRAS G12C, a major promoter of cancer development in people with this genetic mutation.

The following are particular Sotorasib indications:

1. Carcinoma of the non-small cell lung (NSCLC) with the KRAS G12C mutation.

2. Disease development following previous therapy(s).

3. Individuals who cannot have surgery or get radiation therapy.

Dose

1. Sotorasib should be taken orally once a day, with or without meals, at doses of 960 mg. The pills of Sotorasib should be eaten whole with a glass of water while taking them. Depending on the patient's unique condition and reaction to treatment, as well as any additional drugs or medical problems, the dose and length of the course of treatment may change.

2. It is crucial to take Sotorasib exactly as advised. Without seeing a doctor, do not alter the Sotorasib dosage or stop taking medication altogether, as this might reduce its efficacy and raise the chance of experiencing adverse effects.

Pharmacology

Mechanism of Action:

1. By activating the protein and promoting effectors in the MAP kinase pathway, GTP normally binds to KRAS.

2. KRAS is deactivated, and GTP hydrolyzes to GDP.

3. KRAS G12C mutations prevent GTP from being hydrolyzed, leaving it active.

4. With KRAS G12C mutations, Sotorasib binds to the cysteine residue, keeping the protein inactive.

5. As the natural type, KRAS lacks the cysteine residue that Sotorasib targets, so off-target effects are avoided. One to three percent of solid tumors, Three percent of colorectal and appendix cancers, and 13 percent of non-small cell lung cancers have this mutation.

Absorption

Sotorasib is absorbed at 960 mg once daily, with a Cmax of 7.50 g/mL, a median Tmax of 2.0 hours, and an AUC0-24 h of 65.3 h*g/mL.

Volume of Distribution

The Sotorasib distribution volume is 211 Liter.

Involving Proteins

In plasma, Sotorasib is 89 percent protein-bound.

Metabolism

The two main metabolic pathways for Sotorasib are conjugation and CYP3As.

Method of Exclusion

74 percent of the drug Sotorasib is excreted in feces, while 6 percent is excreted in the urine.

The unmodified parent molecule makes up 53 percent of the dosage found in the feces and one percent of the dose found in the urine.

Half-Life

The terminal elimination half-life of Sotorasib is 5.5 +/- 1.8 hours.

Clearance

At a steady state, Sotorasib has an apparent clearance of 26.2 liters per hour.

Management of Toxicity

Depending on the toxicity and the circumstances surrounding each patient, Sotorasib's clinical and non-clinical side effects may require different management strategies. Following are some basic toxicity management guidelines:

Managing Clinical Toxicity:

1. When mild to severe side effects like diarrhea or nausea occur, supportive care techniques like water or anti-nausea medication are frequently used to control them.

2. Treatment options for more severe side effects, such as pneumonitis or elevated liver enzymes, may include stopping Sotorasib usage and/or administering corticosteroids or other immunosuppressive drugs.

3. Healthcare professionals must regularly evaluate patients for negative side effects and modify therapy as necessary.

Management of Non-clinical Toxicity

1. Similar to clinical toxicity, non-clinical toxicity management is based on the degree of toxicity and the circumstances of each patient.

2. Patients may need to be watched for indications of DNA (deoxyribonucleic acid) damage or an increased risk of developing cancer if Sotorasib is determined to have genotoxic potential.

3. Treatment options for liver toxicity may include monitoring liver function tests, modifying doses as needed, or stopping the medicine altogether.

4. It may be important to refrain from using Sotorasib in pregnant women or those attempting to get pregnant in situations of developmental toxicity.

Warnings and Precautions

When taking Sotorasib, the following warnings and precautions are crucial to remember:

1. Interstitial Lung Disease (ILD): Sotorasib may result in interstitial lung disease (ILD), a severe and potentially deadly illness. ILD symptoms might include fever, coughing, and shortness of breath. Sotorasib therapy should be stopped after ILD is detected, and suitable medical attention should be given.

2. Hepatotoxicity: Sotorasib has the potential to damage the liver, which might result in liver failure. When taking Sotorasib, liver function tests should be performed frequently, and the medication should be stopped if liver damage is detected.

3. Embryo-Fetal Toxicity: Sotorasib can damage a growing baby and should not be taken during pregnancy unless the possible advantages outweigh the dangers due to embryo-fetal toxicity. Patients should use reliable birth control while using Sotorasib and for at least a month after finishing the medication.

4. QT Prolongation: Sotorasib has the potential to extend QT, which may result in an irregular heartbeat. When using Sotorasib, patients with a history of QT prolongation or other risk factors for this illness should be constantly monitored.

5. Rash: Sotorasib may result in a serious rash. Sotorasib therapy should be stopped, and proper medical attention should be given if a severe rash appears.

6. Photosensitivity: Sotorasib has the potential to cause photosensitivity, which might result in a painful sunburn. With Sotorasib therapy, patients should stay out of the sun and wear sunscreen and protective clothing.

7. Usage in Certain Populations: As the safety and effectiveness of Sotorasib have not been demonstrated in patients with moderate or severe renal impairment, these patients should take it with caution.

Contraindications:

1. Hypersensitivity: Those with a known allergy to the medication or its ingredients should not use Sotorasib.

2. Strong CYP3A4 Inhibitors: Sotorasib should not be administered to individuals who are using strong CYP3A4 inhibitors since these medications can raise the blood concentration of Sotorasib and increase the risk of side effects.

3. Pregnancy: Due to the possibility of damage to a developing baby, Sotorasib is not recommended for use in pregnant women.

4. Breastfeeding: Because it is unknown if Sotorasib is secreted in human milk and might affect a nursing child, the medicine is contraindicated for breastfeeding women.

5. Severe Hepatic Impairment: Those with severe hepatic impairment shouldn't take Sotorasib because it hasn't been thoroughly researched in this group and may worsen their liver damage.

Other Specifications:

Pregnancy: Sotorasib should not be used during pregnancy due to the risk to the fetus. Effective contraception should be used by women who are sexually active during their Sotorasib therapy and for at least one month following the final dosage.

Lactation: It is unknown if Sotorasib is secreted in breast milk during lactation. Therefore, breastfeeding should be avoided while receiving Sotorasib medication due to the risk of damage to a nursing newborn.

Pediatrics: The safety and efficacy of Sotorasib in pediatric patients under 18 have not been demonstrated. Sotorasib is not advised for usage in this demographic until further information is known.