INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS • loo-ma-krass
SOTORASIB • soh-toh-rass-ib
About KRAS G12C
Prevalence
KRASG12C inhibition
Efficacy
CodeBreaK 100
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Why to test

Patients with KRAS G12C–mutated locally advanced or metastatic NSCLC have an actionable mutation and may be eligible for LUMAKRAS® (sotorasib) following first line of therapy1

KRAS G12C is one of the most prevalent oncogenic drivers in NSCLC with a prevalance of ~ 13%2

NCCN Clinical Practice Guidelines in Oncology

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for KRAS in all eligible patients with advanced NSCLC3,*,†,‡

  • Testing is recommended at diagnosis via a broad, panel-based approach
CAP/IASLC/AMP/ASCO Guidelines

CAP/IASLC/AMP and ASCO Guidelines recommend testing for actionable biomarkers (eg, KRAS) utilizing either a comprehensive panel or targeted testing1,4

KRAS mutation

KRAS mutations are truncal, generally occur early, and are stable throughout the course of the disease, as opposed to other mutations, like EGFR T790M, that may develop over time5

Consider testing and documenting results for all eligible patients
with NSCLC for KRAS G12C at diagnosis to inform treatment plan decisions6,7

A separate real-world study evaluating patients from 2015–2021 demonstrated that, despite increased adoption of NGS-based testing over time, roughly 1 in 3 patients with non-squamous advanced or metastatic NSCLC in the US didn’t receive comprehensive NGS testing by 20208

32% of NSCLC patients 32% of NSCLC patients
32% of NSCLC patients

of all NSCLC patients in the study didn't receive comprehensive NGS testing

  • In a real-world, retrospective study conducted from January 2015 to March 2021 of 17,513 adult patients with advanced or metastatic NSCLC who had received systemic anticancer therapy within 90 days of diagnosis, researchers evaluated patients’ electronic health records to measure biomarker testing rates of any kind, including any test modality such as NGS, FISH, IHC, and PCR. Throughout the study period, 8,321 patients received NGS testing; in 2020, 1,638 out of a total of 2,406 patients received NGS testing8

Be a biomarker testing steward—consider testing eligible patients for all
actionable biomarkers at diagnosis of advanced NSCLC

Biomarker testing in NSCLC may be underutilized in certain populations

Microscope
  • In a real-world database, only 29.7% (n=922) of Black/African American patients received NGS testing vs 36.6% (n=6,705) of White patients before first-line therapy9,§
    • 43.8% (n=922) of Black/African American patients received NGS testing vs 54.7% (n=6,705) of White patients at any time after diagnosis9,§
Cigarette
  • While KRAS mutations are most commonly found in smokers, they can occur regardless of smoking status, clinical or demographic characteristics5

Help ensure all patient populations have access to precision medicine and
appropriate targeted therapies. Test all eligible patients

As a leader in KRAS science, Amgen continues to partner with the scientific community to advance precision medicine

Watch this video for an expert perspective on KRAS G12C testing

Expert Perspectives: A Case-Based Discussion on KRAS G12C Testing

Join Dr Michelle Shiller, a molecular genetic pathologist at Baylor University, as she discusses different clinical scenarios in NSCLC and key considerations for KRAS G12C testing.

Plan for tomorrow today. Consider testing and documenting
your patient's KRAS G12C status as a first step

Learn about KRAS G12C best practices for
documenting biomarker test results


*The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.3

†It is recommended at this time that, when feasible, testing be performed via a broad, panel-based approach, most typically performed by NGS.3

‡Does not include locally advanced.3

§This study used the Flatiron EHR-derived deidentified database to evaluate a total of 10,333 patients with an advanced/metastatic non-squamous NSCLC diagnosis on or after January 1, 2017. 7,627 of the patients were of White (n=6,705) or Black/African American (n=922) descent. The study included patients who received treatment within 120 days, and excluded patients with additional cancers and those who died within 120 days of diagnosis. Biomarker testing included ALK, EGFR, ROS1, KRAS, and BRAF and included all single-gene and NGS-based tests, and was evaluated within 10 days of advanced/metastatic diagnosis.9

ALK , anaplastic lymphoma kinase; AMP, Association for Molecular Pathology; ASCO, American Society of Clinical Oncology; BRAF, proto-oncogene B-Raf; CAP, College of American Pathologists; EGFR, epidermal growth factor receptor; EHR, electronic health record; FISH, fluorescence in situ hybridization; IASLC, International Association for the Study of Lung Cancer; IHC, immunohistochemistry; KRAS, Kirsten rat sarcoma viral oncogene homolog; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction; ROS1, c-ros oncogene.

How to test

KRAS G12C can be detected in tissue and liquid biopsy specimens using well-validated common molecular testing methods10,11

KRAS G12C mutation

When ordering single-gene biomarker tests, consider adding KRAS G12C or switching to a panel

  • Check your current panel—most already include KRAS G12C11
    • Patient OOP cost will vary depending on patient’s insurance. Average patient OOP cost: $0 for original Medicare and $65 for commercially insured patients12,13,*
Multidisciplinary medical team
Multidisciplinary medical team

When testing your patient's biomarker status, consider consulting your entire multidisciplinary team to help facilitate the ordering, documentation, and retrieval of biomarker testing

*Cost estimates herein are for informational purposes only and may not actually represent what patients ultimately pay for certain tests. Further, it should not be construed as any statement, promise, or guarantee by Amgen concerning coverage and/or levels of reimbursement, payment, or charge. Laws, regulations, and policies concerning reimbursement are complex and are updated frequently.

Liquid biopsy can be used as an alternative to tissue testing14,15

Syringe
  • Liquid biopsy may identify actionable mutations like KRAS G12C when tissue quantity is not sufficient14
Test tube and cfDNA
  • NCCN Guidelines state that cfDNA testing can be used when a patient is medically unfit for tissue biopsy and/or insufficient tissue is available for molecular analysis, or can be used in conjunction with tissue-based testing3,†,‡
Clipboard
  • The CAP/IASLC/AMP guidelines and an IASLC consensus paper support the utility of positive tissue and liquid biopsy results to inform treatment plan decisions14,16
48%
  • Tissue biopsy is the gold standard for biomarker testing; however, using cfDNA in addition to tissue resulted in a 48% increase in the identification of patients with a guideline-recommended biomarker10,§
Test results
  • Because of variable tumor shedding and assay sensitivity, confirming negative liquid biopsy results with tissue biopsy is recommended as mutations cannot be ruled out from a liquid sample alone14

†The NCCN Guidelines for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.3

‡It is recommended at this time that, when feasible, testing be performed via a broad, panel-based approach, most typically performed by NGS.3

§In the NILE study of 282 patients with non-squamous mNSCLC who received SOC tissue genotyping and cfDNA analysis for guideline-recommended biomarkers, including KRAS, between 2016 and 2018. Overall concordance across four genes (EGFR exon 19 deletion and L858R, ALK fusion, ROS1 fusion, and BRAF V600E).10

ALK, anaplastic lymphoma kinase; AMP, Association for Molecular Pathology; BRAF, proto-oncogene B-Raf; CAP, College of American Pathologists; cfDNA, circulating free DNA; EGFR, epidermal growth factor receptor; IASLC, International Association for the Study of Lung Cancer; KRAS, Kirsten rat sarcoma viral oncogene homolog; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; OOP, out of pocket; ROS1, c-ros oncogene; SOC, standard-of-care.

FDA-approved tissue and liquid companion diagnostics are available to test for KRAS G12C**

Tissue PCR

Qiagen logo
Therascreen logo

Liquid NGS

Guardant 360 CDx logo

www.qiagen.com/KRAS

Download testing information

Click here to download
QIAGEN therascreen® KRAS RGQ PCR Kit

Liquid NGS

Guardant 360 CDx logo

www.guardant360cdx.com

Download testing information

Click here to download
Guardant360® CDx

**Information on FDA-approved tests can be found at https://www.fda.gov/medical-devices/products-and-medical-procedures/vitro-diagnostics.

Call your lab and ask about your patients’ KRAS G12C status

There are differences in how reports may list KRAS G12C17,18

Observation

There are various ways that KRAS G12C mutations can be reported, such as 12Cys, Gly12Cys (GGT or TGT), c.34G>T, or p.G12C

Suggestion

For ease of interpretation, consider noting KRAS G12C in the synopsis of your report

Sample report of KRAS G12C testing Sample report of KRAS G12C testing
 

When documenting and accessing patients’ test results consider the following:

  • Append patients’ biomarker test reports in a reliable location within their EMR, such as with their surgical pathology report
  • Consider documenting KRAS G12C status in a structured field in EMRs to allow results to be word text searchable
  • Establish the optimal location for test results with your multidisciplinary team for easy retrieval by providers, now and in the future
  • Look at prior pathology results and add patients’ KRAS G12C status to clinical notes
  • Call your lab or access the lab portal if test results cannot be located
  • Call your lab if test results cannot be located

When thinking about your practice, consider:

Does your patient receive their test results in their patient portal?

Are your lab results integrated into your EMR and is it in an easily accessible and consistent location?

Do you have any other tools, like an app, to help keep track of and access your patient's test results?

CDx, companion diagnostic; EMR, electronic medical record; PCR, polymerase chain reaction.

Consider documenting and keeping track of test results for
all actionable biomarkers for future reference

Are you looking for information on patient characteristics
from the pivotal CodeBreaK 100 Phase 2 trial?

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
  • Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100 ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
  • Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most common adverse reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full LUMAKRAS Prescribing Information.

References: 1. The Galien Foundation. https://www.prnewswire.com/news-releases/the-galien-foundation-honors-2022-prix-galien-award-recipients-301662219.html. Accessed December 6, 2022. 2. LUMAKRAS® (sotorasib) prescribing information, Amgen. 3. Canon J, et al. Nature. 2019;575(7781):217-223. 4. Data on file, Amgen; [Most prescribed chart audit]. 5. Data on file, Amgen; [Unique patients]. 6. Data on file, Amgen; [Unique prescribers]. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v.1.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed December 21, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 8. Sotorasib CSR. Amgen; 2021. 9. The Galien Foundation. https://www.galienfoundation.org/what-you-must-know. Accessed December 6, 2022. 10. The Galien Foundation. https://candidates.prix-galien-usa.com/submissions/eligibility. Accessed December 1, 2022.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS®. LUMAKRAS® was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS® can cause ILD/pneumonitis that can be fatal.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS® was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS® in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS® if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug Interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS®.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS® 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full LUMAKRAS® Prescribing Information.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS®. LUMAKRAS® was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS® can cause ILD/pneumonitis that can be fatal.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS® was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS® in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS® if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug Interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS®.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS® 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full LUMAKRAS® Prescribing Information.

Important Safety Information

Hepatotoxicity

  • LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
  • Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Important Safety Information

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS®. LUMAKRAS® was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/ increased aspartate aminotransferase (AST); of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS®. LUMAKRAS® was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.