2024 MIPS Measure #451: RAS (KRAS and NRAS) Gene Mutation Testing Performed for Patients with Metastatic Colorectal Cancer Who Receive Anti-epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody Therapy

Quality ID 451
NQF 1859
High Priority Measure No
Specifications Registry
Measure Type Process
Specialty Oncology/Hematology

Measure Description

Percentage of adult patients (aged 18 or over) with metastatic colorectal cancer who receive anti-epidermal growth factor receptor monoclonal antibody therapy for whom RAS (KRAS and NRAS) gene mutation testing was performed.



This measure is to be submitted once per performance period for patients with colorectal cancer seen during the performance period. This measure may be submitted by Merit-based Incentive Payment System (MIPS) eligible clinicians who perform the quality actions described in the measure based on the services provided and the measure-specific denominator coding.

Measure Submission Type:

Measure data may be submitted by individual MIPS eligible clinicians, groups, or third-party intermediaries. The listed denominator criteria are used to identify the intended patient population. The numerator options included in this specification are used to submit the quality actions as allowed by the measure. The quality data codes listed do not need to be submitted by MIPS eligible clinicians, groups, or third-party intermediaries that utilize this modality for submissions; however, these codes may be submitted for those third-party intermediaries that utilize Medicare Part B claims data. For more information regarding Application Programming Interface (API), please refer to the Quality Payment Program (QPP) website.



Adult patients with metastatic colorectal cancer who receive anti-EGFR monoclonal antibody therapy

Denominator Criteria (Eligible Cases):

Patients aged ≥ 18 years on date of encounter


Diagnosis of initial colon or rectal cancer (ICD-10 CM): C18.0, C18.2, C18.3, C18.4, C18.5, C18.6, C18.7, C18.8, C18.9, C19, C20


At least two patient encounters during the performance period (CPT): 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215


Telehealth Modifier (including but not limited to): GQ, GT, 95, POS 02, POS 10


Patient has metastatic disease at diagnosis: G9838


Anti-EGFR monoclonal antibody therapy: G9839



RAS (KRAS and NRAS) gene mutation testing performed before initiation of anti-EGFR MoAb


RAS mutation testing - RAS testing for this measure refers to assays that detect mutations in codons 12 and 13 of exon 2, codons 59 and 61 of exon 3 and codons 117 and 146 in exon 4 in KRAS or NRAS. Do not include results from mutations at other codons or assays for other alterations (e.g., BRAF, PI3K, PTEN genes). The College of American Pathologists (CAP) Perspectives on Emerging Technology (POET) Report on RAS mutation testing provides additional guidance on testing.

If multiple RAS mutation tests have been performed, refer to the most recent test results.

Anti-EGFR monoclonal antibody includes cetuximab or panitumumab.

Numerator Instructions:

In the absence of any documentation regarding testing for the RAS (KRAS and NRAS) gene mutation, submit G9841: RAS (KRAS and NRAS) gene mutation testing not performed before initiation of anti-EGFR MoAb. Report G9840: RAS (KRAS and NRAS) gene mutation testing performed before initiation of antiEGFR MoAb, if the report indicates a mutation within codons 12 and 13 of exon 2, codons 59 and 61 of exon 3 and codons 117 and 146 in exon 4 in KRAS or NRAS, where KRAS or NRAS gene was detected in the DNA extracted from the colon tumor specimen.

Numerator Options:

Performance Met: RAS (KRAS and NRAS) gene mutation testing performed before initiation of anti-EGFR MoAb (G9840)


Performance Not Met: RAS (KRAS and NRAS) gene mutation testing not performed before initiation of anti-EGFR MoAb (G9841)



The American Society of Clinical Oncology (ASCO) envisions that use of this measure will improve concordance with recommendations for RAS (KRAS and NRAS) testing for patients with metastatic colorectal cancer. We recognize the importance of ensuring that the appropriate patient population receives guideline concordant treatment as studies demonstrate that the administration of EGFR-targeted therapies, specifically cetuximab or panitumumab, offer no clinical benefit to patients diagnosed with KRAS-mutated or NRAS-mutated tumors. Clinical trial data strongly suggest that patients with RAS mutations are better served with other targeted therapies, especially considering the harms and costs of anti-EGFR treatment. Therefore, the measure focus is on halting use of antiEGFR MoAb therapies in patients who will not derive any benefit.


Clinical Recommendation Statements

This measure is based on ASCO and National Comprehensive Cancer Network (NCCN) Guidelines:

“Colorectal carcinoma patients being considered for anti-EGFR therapy must receive RAS mutational testing. Mutational analysis should include KRAS and NRAS codons 12, 13 of exon 2; 59, 61 of exon 3; and 117 and 146 of exon 4 (“expanded” or “extended” RAS)”.

Sepulveda AR, Hamilton SR, Allegra CJ, et al: Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. Journal of Clinical Oncology 35:1453-1486, 2017.

“All patients with metastatic colorectal cancer should have tumor genotyped for RAS (KRAS and NRAS) and BRAF mutations individually or as part of an NGS panel. Patients with any known KRAS mutation (exon 2, 3, 4) or NRAS mutation (exon 2, 3, 4) should not be treated with either cetuximab or panitumumab. BRAF V600E mutation makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor.”

“A sizeable body of literature has shown that tumors with a mutation in exons 2, 3, or 4 of either the KRAS or NRAS genes are essentially insensitive to cetuximab or panitumumab therapy. The panel therefore strongly recommends RAS (KRAS/NRAS) genotyping of tumor tissue (either primary tumor or metastasis) in all patients with mCRC. Patients with known KRAS or NRAS mutations should not be treated with either cetuximab or panitumumab, either alone or in combination with other anticancer agents, because they have virtually no chance of benefit and the exposure to toxicity and expense cannot be justified (NCCN 2022).

ASCO released a Provisional Clinical Opinion Update on extended RAS testing in patients with mCRC that is consistent with the NCCN Panel’s recommendations. A guideline on molecular biomarkers for CRC developed by the ASCP, CAP, AMP and ASCO also recommends RAS testing consistent with the NCCN recommendations” (NCCN 2022).

NCCN Clinical Practice Guidelines in Oncology™. Colon Cancer, V.2.2022 https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf

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