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).

Why to test

Patients with KRAS G12C–mutated locally advanced or metastatic NSCLC now have an actionable mutation that could be eligible for LUMAKRAS™ following first line of therapy1

KRAS G12C and EGFR make up ~ 75% of all actionable driver mutations in NSCLC1,2

Guidelines

CAP/IASLC/AMP and ASCO Guidelines recommend testing for actionable biomarkers (eg, KRAS) utilizing either a comprehensive panel or targeted testing1,3

DNA

Consider testing all eligible patients with NSCLC for KRAS G12C at diagnosis

  • While KRAS mutations are most commonly found in smokers, they can occur regardless of clinical or demographic characteristics4
  • KRAS mutations occur early and are generally stable throughout the course of the disease, as opposed to other mutations, like EGFR T790M, that may develop over time5,6

AMP, Association for Molecular Pathology; ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists; EGFR, epidermal growth factor receptor; IASLC, International Association for the Study of Lung Cancer; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer.

How to test

KRAS G12C can be detected in tissue and liquid biopsy specimens using well-validated common molecular testing methods7,8

microscope

Most NGS panels already include KRAS G12C8

  • Patient OOP cost will vary depending on patient’s insurance. $0 average patient out-of-pocket for original Medicare and $65 for commercially insured patients9,10,*
KRAS molecule

When ordering single-gene biomarker tests, consider adding KRAS G12C

Liquid testing

Liquid biopsy has high degrees of concordance with tissue-based testing, with 93% concordance for KRAS mutations in patients with mNSCLC7

  • Consistent efficacy results were seen in patients with KRAS G12C mutation identified in either tissue or plasma specimens11
DNA

For Pathologists: FFPE tissue is gold standard. You can test for KRAS G12C using NGS, PCR, and Sanger sequencing methods7,8

  • CAP/IASLC/AMP Guidelines also support the use of cytopathology specimens6

Call your lab and ask about your patient’s KRAS G12C status

*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.

FFPE, formalin-fixed, paraffin-embedded; mNSCLC, metastatic non-small cell lung cancer; NGS, next-generation sequencing; OOP, out of pocket; PCR, polymerase chain reaction.

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

Tissue PCR

Companion diagnostics
Companion diagnostics
www.qiagen.com/KRAS

Liquid NGS

Companion diagnostics
www.guardant360cdx.com

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

Click here to download factsheets for more information on these tests

Download

QIAGEN therascreen® KRAS RGQ PCR Kit

Download

Guardant360® CDx

Reporting considerations for pathologists

Reporting KRAS mutations, and specifically KRAS G12C, can vary across tumor types

DNA

In other tumor types, KRAS is sometimes reported as mutant or wild-type without specifying the variant12


KRAS wild-type or KRAS mutant KRAS wild-type or KRAS mutant
Lungs

In NSCLC, specific KRAS mutations should be reported at the variant level13,‡

KRAS G12C or KRAS G12D or KRAS G12V KRAS G12C or KRAS G12D or KRAS G12V

There are differences in how reports may list KRAS G12C13

Observation

There are various ways that KRAS G12C mutations can be reported, such as Gly12Cys or 12Cys14

Suggestion

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

Sample Biomarker Test Report Sample Biomarker Test Report

In NSCLC, consider reporting KRAS at the variant level and consider updating your test requisition forms to show KRAS includes the G12C point mutation

Not comprehensive of all possible variants.

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 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.