By Aileen Anglin, APRN, ACNP-BC, AOCNP®, and Amber Dittfurth, BSN, RN, OCN®
After clinical trials demonstrated a 43% durable objective response rate with a median 8.5-month duration, the U.S. Food and Drug Administration (FDA) granted adagrasib (Krazati™) accelerated approval in December 2022 for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C variant, as detected by an FDA-approved test, whose disease has progressed on or after at least one prior systemic therapy.
Mechanism of Action
Adagrasib inhibits a variant form of KRAS called KRAS G12C. Adagrasib bonds with and inactivates the variant KRAS G12C cysteine protein, rendering the cells less viable, stopping the tumor’s ability to proliferate, and leading to tumor regression.
Adult patients with locally advanced or metastatic NSCLC who have received one prior systemic therapy and have a KRAS G12 variant confirmed by an FDA-approved test.
Dosing and Administration
Take 600 mg by mouth twice daily until you experience disease progression or unacceptable toxicity. Swallow the medication whole at the same time every day, with or without food. Do not crush, split, or chew the medication. If you miss a dose by more than four hours or vomit a dose, wait and take the next dose at the next scheduled time.
The most common adverse reactions reported in at least 25% of patients in the drug’s clinical trials were nausea, vomiting, diarrhea, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, and decreased appetite. The most common severe (grade 3 or 4) adverse reactions reported in more than 2% of patients were lab abnormalities such as decreased lymphocytes, decreased hemoglobin, increased ALT/AST, hypokalemia, hyponatremia, increased lipase, decreased leukocytes/neutrophils, and increased alkaline phosphatase. The package insert contains warnings for gastrointestinal adverse reactions (bleeding, obstruction, colitis, ileus, stenosis, nausea, diarrhea, and vomiting), QTc interval prolongation, hepatotoxicity, and interstitial lung disease/pneumonitis.
Adagrasib may cause infertility. Patients should not breastfeed while on adagrasib and up to one week after last dose. Avoid concomitant use with strong CYP3A inducers and strong CYP3A inhibitors until approximately eight days after starting adagrasib. Adagrasib may have an impact on several other medications; ensure the patient’s medication list is current prior to starting and during therapy with adagrasib. Because of the risk of QTc prolongation, obtain a baseline electrocardiogram and electrolyte panel prior to starting adagrasib; ongoing monitoring may be indicated for patients taking other medications that cause QTc prolongation or who have congestive heart failure, bradyarrhythmias, or electrolyte abnormalities. Monitor liver function tests prior to starting adagrasib and monthly for three months or as clinically indicated.
Teach patients to maintain adequate hydration; use antidiarrheals; manage nausea, vomiting and, fatigue; and report signs of hepatotoxicity or respiratory symptoms that may indicate interstitial lung disease or pneumonitis.
No differences were seen in safety or effectiveness in patients aged 65 or older compared to younger patients.
Mirati and Me is available online or by phone at 844-MIRATI2 (844-647-2842).