The US Food and Drug Administration (FDA) recently approved a new medication, sotorasib (Lumakras), for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) that harbors a KRAS G12C mutation and who have been on at least 1 prior therapy.1 This mutation is found in approximately 13% of NSCLCs, and sotorasib is the first medication granted approval that targets this mutation.1 Understanding the dosing and potential side effects is important to provide patient education and ensure compliance with this first-in-class medication.
Efficacy of sotorasib was evaluated in the CodeBreaK100 trial, a study comprising 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after undergoing treatment with an immune checkpoint inhibitor and/or platinum-based chemotherapy. Sotorasib was approved using the Accelerated Approval. Sotorasib also was granted Fast Track, Priority Review, and Breakthrough Therapy designations.1
Dosing and Interactions
Sotorasib is taken by mouth, once a day, and comes in 120-mg tablets. With a starting dose of 920 mg once a day, a patient will take 8 tablets daily. The tablets should be swallowed whole, not crushed or broken. This medication can be taken with or without food, and needs to be taken around the same time each day.
A missed dose can be taken up to 6 hours after the missed time. However, once outside the 6-hour window, the dose should be skipped. Patients should not double-up the next day’s dose.
If the 920-mg dose is not tolerated, it can be reduced to 480 mg once a day, and again to 240 mg once a day. If the patient cannot tolerate the 240-mg dose, sotorasib should be discontinued.2
Stomach acid reducing medications, such as proton pump inhibitors or H2 blockers, can alter absorption of sotorasib, so concomitant use should be avoided. If acid reducing medication is required, an antacid may be taken. However, sotorasib should be taken at least 4 hours before and 10 hours after taking the antacid.2
The CodeBreaK100 trial also demonstrated an interaction with digoxin. Taking sotorasib along with digoxin was found to increase the levels of digoxin in the blood, which could cause significant side effects. Dose reductions of digoxin may be required and should be discussed with the digoxin prescriber before starting sotorasib.2
As with all medications, sotorasib has the potential to cause side effects. In the CodeBreaK100 trial, 9% of patients experienced side effects that led to permanent discontinuation of the medication. The most common side effects were diarrhea, musculoskeletal pain, nausea, fatigue, and cough.3
Diarrhea In the CodeBreaK 100 trial, 42% of patients experienced diarrhea.2 To manage diarrhea, patients should be encouraged to follow a bland or BRAT (bananas, rice, applesauce, toast) diet and to maintain adequate hydration. The use of loperamide to treat diarrhea may also be necessary. If the patient’s diarrhea becomes severe and cannot be managed with standard therapy, sotorasib should be held and resumed at a lower dose when diarrhea improves to baseline or grade 1.4
Musculoskeletal pain Of the trial participants, 35% experienced musculoskeletal pain.2 Patients should keep a diary of any pain they experience to help identify potential triggers or times of the day when the pain occurs. Depending on the severity of pain, medications or other interventions such as applying heat or ice to the affected areas may be required to achieve patient comfort.4
Nausea Twenty-six percent of the participants experienced nausea.2 Nausea can be managed through nonpharmaceutical interventions such as eating a bland diet, avoiding fried or greasy foods, and eating smaller meals.4 Pharmaceutical interventions such as antiemetics may be necessary. If grade 3 or 4 nausea and vomiting occur and cannot improve despite the use of antiemetics and other interventions, sotorasib should be held until symptoms improve to grade 1 or better, then resumed at a lower dose.2
Fatigue Twenty-six percent of trial participants experienced fatigue.2 Interventions to help manage fatigue include light exercise and activity as tolerated, and grouping tasks or activities together or spreading them throughout the day to manage energy levels.4 Other interventions include educating patients on good sleep and wake cycles can be helpful as well.
Cough The patient should monitor their cough patterns, and report to the oncology team their frequency and severity. Pharmacological interventions for cough, such as antitussives, may be required.4
Serious Adverse Effects
Two serious adverse effects were reported with the use of sotorasib: hepatotoxicity and interstitial lung disease (ILD).2
Hepatotoxicity Twenty-five percent of trial participants experienced liver dysfunction, resulting in elevated hepatic transaminases, elevated bilirubin, and drug-induced hepatitis. Liver function tests should be performed before starting sotorasib and every 3 weeks for the first 3 months, then once a month. Liver function tests should include AST, ALT, and bilirubin levels.2 Patients should be instructed to report signs or symptoms of liver dysfunction such as abdominal pain, jaundice, dark urine, or itching to their oncology team.4 Sotorasib should be held if a patient develops grade 2, 3, or 4 hepatotoxicity until the symptoms resolve to a grade 1 or better, and then resumed at a lower dose.2
Interstitial lung disease Although ILD was rare, several trial participants developed the condition. Patients should be evaluated regularly for respiratory symptoms such as shortness of breath, cough, and fever, and should be encouraged to quickly report these symptoms to their healthcare team. If ILD is suspected, sotorasib should be held while the patient undergoes work-up for their symptoms.
Sotorasib was granted an Accelerated Approval. As part of this program, further study is required to verify and describe anticipated clinical benefits. Research is ongoing to determine if a lower dose of sotorasib will provide the same clinical benefit.1
- US Food and Drug Administration. FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy [news release]. US Food & Drug Administration website. Posted May 28, 2021. Accessed July 22, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-lung-cancer-mutation-previously-considered-resistant-drug
- Lumakras™ [prescribing information]. Thousand Oaks, CA: Amgen; May 2021. Accessed July 22, 2021. https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/lumakras/lumakras_pi_hcp_english.ashx
- Amgen. Adverse reactions. Thousand Oaks, CA: Amgen; May 2021. Accessed July 22, 2021. https://www.lumakrashcp.com/sotorasib-safety
- Amgen. Your guide to Lumakras (sotorasib) 120 mg tablets. Thousand Oaks, CA: Amgen; May 2021. Accessed July 22, 2021. https://www.lumakrashcp.com/-/media/Themes/Amgen/Lumakrashcp-com/Lumakrashcp-com/pdf/LumakrasDigitalBrochure.pdf