RAS (KRAS and NRAS) Gene Mutation Testing Performed for Patients with

Measure Specification

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 anti-EGFR MoAb therapies in patients who will not derive any benefit.

This measure is based on ASCO and National Comprehensive Cancer Network (NCCN) Guidelines: “Anti-EGFR therapy is not recommended for patients with RAS-mutant mCRC” (Morris, et al., 2023). “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, et al.

, 2017). “All patients with metastatic CRC should have tumor genotyped for RAS (KRAS and NRAS) and BRAF mutations individually or as part of a next-generation sequencing (NGS) panel (preferred). Patients with any known KRAS mutation (exons 2, 3, and 4) or NRAS mutation (exons 2, 3, and 4) should not be treated with either cetuximab or panitumumab, unless given as part of a regimen targeting a KRAS G12C mutation.

BRAF V600E mutation makes response to panitumumab or cetuximab highly unlikely unless given with a BRAF inhibitor” (NCCN, 2025). “A sizable 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 (either primary tumor or metastasis) in all patients with mCRC.

Patients with known KRAS- or NRAS-mutant tumors 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, 2025). 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, 2025).

This measure contains one strata defined by a single submission criteria. This measure produces a single performance rate. For the purposes of MIPS implementation, this patient-process measure is submitted a minimum of once per patient during the performance period. The most advantageous quality data code will be used if the measure is submitted more than once. In the absence of any documentation regarding testing for the RAS (KRAS and NRAS) gene mutation, submit performance not met.