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Analysis of KRAS Status

Last Review Date: August 8, 2025 
Number: MG.MM.LA.19bC4

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Definitions KRAS gene A type of oncogene that encodes the RAS protein predisposed to mutations that result in a constitutively activated protein. The activated protein is implicated in various malignancies, including colorectal carcinoma, lung adenocarcinoma, and ductal carcinoma of the pancreas, and may cause tumor resistance to epidermal growth factor receptor inhibitors. KRAS sequence variant analysis A tool used to predict an individual’s response to anti EGFR drug therapy for conditions including metastatic colorectal cancer and anal cancer. KRAS mutation status
A mutation at codon 12 or 13 of the KRAS gene. The presence of a KRAS mutation correlates with lack of response to anti-EGFR therapy with cetuximab or with panitumumab. Screening for KRAS mutations status may be used as a prognostic marker as patients with colorectal cancer and positive KRAS tumors have a worse prognosis. KRAS wild-type status The typical or non-mutated form of the KRAS gene. Tumors with this KRAS type increases the likelihood of a response to anti-EGFR therapy with cetuximab or with panitumumab.

Related Medical Guidelines Erbitux® (cetuximab) Gene Expression Profiling Vectibix® (panitumumab)

Guideline Analysis of KRAS status in members with non-small cell lung cancer, stage IV colon cancer, rectal cancer, colorectal cancer or anal adenocarcinoma is considered medically necessary to predict response to Lumakras (sotorasib), Erbitux (cetuximab) or Vectibix (panitumumab) prior to initiation of therapy.

Limitations/Exclusions Analysis of KRAS status is considered investigational and not medically necessary for all other indications that do not meet the above criteria.

Revision History 9/10/2021 Lumakras (sotorasib) added to list of drugs for which KRAS analysis prior to initiation of therapy is warranted 10/14/2016 Added non-small cell lung cancer as covered indication

Applicable Procedure Codes 81275 KRAS (Kirsten rat sarcoma viral oncogene homolog) (eg, carcinoma) gene analysis; variants in exon 2 (eg, codons 12 and 13) 81276

KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene) (eg, carcinoma) gene analysis, variants in codons 12 and 13, additional variant(s) (eg, codon 61, codon 146)
81403 Molecular pathology procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of 10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons 88363 Examination and selection of retrieved archival (ie, previously diagnosed) tissue(s) for molecular analysis (eg, KRAS mutational analysis)

Applicable ICD-10 Diagnosis Codes C17.0 Malignant neoplasm of duodenum C17.1 Malignant neoplasm of jejunum C17.2 Malignant neoplasm of ileum C17.3 Meckel's diverticulum, malignant C17.8 Malignant neoplasm of overlapping sites of small intestine C17.9 Malignant neoplasm of small intestine, unspecified C18.0 Malignant neoplasm of cecum C18.2 Malignant neoplasm of ascending colon C18.3 Malignant neoplasm of hepatic flexure C18.4 Malignant neoplasm of transverse colon C18.5 Malignant neoplasm of splenic flexure C18.6 Malignant neoplasm of descending colon C18.7 Malignant neoplasm of sigmoid colon C18.8 Malignant neoplasm of overlapping sites of colon C18.9 Malignant neoplasm of colon, unspecified C19 Malignant neoplasm of rectosigmoid junction C20 Malignant neoplasm of rectum C21.0 Malignant neoplasm of anus, unspecified C21.1 Malignant neoplasm of anal canal C21.2 Malignant neoplasm of cloacogenic zone C21.8 Malignant neoplasm of overlapping sites of rectum, anus and anal canal C33 Malignant neoplasm of trachea

C34.00 Malignant neoplasm of unspecified main bronchus C34.01 Malignant neoplasm of right main bronchus C34.02 Malignant neoplasm of left main bronchus C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung C34.11 Malignant neoplasm of upper lobe, right bronchus or lung C34.12 Malignant neoplasm of upper lobe, left bronchus or lung C34.2 Malignant neoplasm of middle lobe, bronchus or lung C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung C34.31 Malignant neoplasm of lower lobe, right bronchus or lung C34.32 Malignant neoplasm of lower lobe, left bronchus or lung C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung C34.82 Malignant neoplasm of overlapping sites of left bronchus and lung C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung C34.91 Malignant neoplasm of unspecified part of right bronchus or lung C34.92 Malignant neoplasm of unspecified part of left bronchus or lung C77.0 Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck
C77.1 Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes
C77.2 Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes
C77.3 Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes
C77.4 Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes
C77.5 Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes
C77.8 Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions
C77.9 Secondary and unspecified malignant neoplasm of lymph node, unspecified
C78.00 Secondary malignant neoplasm of unspecified lung
C78.01 Secondary malignant neoplasm of right lung
C78.02 Secondary malignant neoplasm of left lung
C78.1 Secondary malignant neoplasm of mediastinum
C78.2 Secondary malignant neoplasm of pleura
C78.30 Secondary malignant neoplasm of unspecified respiratory organ
C78.39 Secondary malignant neoplasm of other respiratory organs
C78.4 Secondary malignant neoplasm of small intestine
C78.5 Secondary malignant neoplasm of large intestine and rectum
C78.6 Secondary malignant neoplasm of retroperitoneum and peritoneum
C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct
C78.80 Secondary malignant neoplasm of unspecified digestive organ
C78.89 Secondary malignant neoplasm of other digestive organs
C79.00 Secondary malignant neoplasm of unspecified kidney and renal pelvis
C79.01 Secondary malignant neoplasm of right kidney and renal pelvis
C79.02 Secondary malignant neoplasm of left kidney and renal pelvis
C79.10 Secondary malignant neoplasm of unspecified urinary organs
C79.11 Secondary malignant neoplasm of bladder
C79.19 Secondary malignant neoplasm of other urinary organs
C79.2 Secondary malignant neoplasm of skin

C79.31 Secondary malignant neoplasm of brain
C79.32 Secondary malignant neoplasm of cerebral meninges
C79.40 Secondary malignant neoplasm of unspecified part of nervous system
C79.49 Secondary malignant neoplasm of other parts of nervous system
C79.51 Secondary malignant neoplasm of bone
C79.52 Secondary malignant neoplasm of bone marrow
C79.60 Secondary malignant neoplasm of unspecified ovary
C79.61 Secondary malignant neoplasm of right ovary
C79.62 Secondary malignant neoplasm of left ovary C79.70 Secondary malignant neoplasm of unspecified adrenal gland
C79.71 Secondary malignant neoplasm of right adrenal gland
C79.72 Secondary malignant neoplasm of left adrenal gland
C79.81 Secondary malignant neoplasm of breast
C79.82 Secondary malignant neoplasm of genital organs
C79.89 Secondary malignant neoplasm of other specified sites
C79.9 Secondary malignant neoplasm of unspecified site
Z85.038 Personal history of other malignant neoplasm of large intestine Z85.048 Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus

References

1. Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti- epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009. http://jco.ascopubs.org/content/27/12/2091.long. Accessed August 11, 2025.
2. Cervantes A, Macarulla T, Martinelli E, et al. Correlation of KRAS status (wild type [wt] vs. mutant [mt]) with efficacy to first-line cetuximab in a study of cetuximab single agent followed by cetuximab + FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol 26: 2008 (May 20 suppl; abstr 4129).
3. Freeman D, Juan T, Meropol NJ, et al: Association of somatic KRAS gene and clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) receiving panitumumab monotherapy. Eur J Cancer Suppl 5: 239, 2007 (abstr O3014)
4. Mao C, Qiu LX, Liao RY et al. KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: a meta-analysis of 22 studies. Lung Cancer 2010; 69(3):272-278.
5. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Colon cancer V4.2025. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed August 11, 2025.
6. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Rectal cancer V2.2025. http://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed August 11, 2025.
7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer V7.2025. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. August 11, 2025.
8. Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006; 6(1-2):17-32.
9. Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 Suppl 3:iii1-9.