RAS Mutations in Metastatic Colorectal Cancer

Prevalence of RAS mutations in mCRC⁴

Roughly 56% of patients with mCRC have a RAS mutation, including nearly 4% of patients with the KRAS variant KRAS G12C⁴

A KRAS variant, KRAS G12C, occurs in 4% of patients with mCRC and may have worse outcomes than other KRAS subtypes^2,4

*Exon 3 mutations included KRAS Q61E, Q61H, Q61K, Q61L, and Q61R. Exon 4 mutations included KRAS A146P, A146T, A146V, and K117N. NRAS mutations included G12A, G12C, G12D, G12F, G12N, G12R, G12S, G12V, G12W, G13C, G13D, G13E, G13R, G13V, Q61E, Q61H, Q61K, Q61L, Q61R, K117N, A146P, A146T, and A146V.⁴

^†This includes samples where information for specific exons and codons were missing while still having overall RAS mutational status.⁴

Compared to other biomarkers, a real-world study suggests that KRAS G12C mutations may be prognostic for poorer outcomes^2,‡

Median OS among patients in the KRAS G12C, KRAS non-G12C, and overall mCRC cohorts²

Median OS of patients with mCRC by variant or subgroup

Despite advances seen in other tumor types, patients with mCRC and RAS mutations such as KRAS G12C have been limited primarily to chemotherapy combinations as treatment, and lack targeted, biomarker-informed approaches^5,6

^‡Estimates of overall survival, based on patients receiving 1L treatment. Other real-world studies of treatment outcomes in KRAS G12C–mutated mCRC have reported mixed results, with some describing poorer prognosis while others describing no difference.^2,7

Due to a lack of targeted options, specific mutational variants like KRAS G12C may be overlooked in mCRC^5,6

Learn more about the role of RAS mutations in mCRC >

2L, second line; BRAF, proto-oncogene B-Raf; CI, confidence interval; KRAS, Kirsten rat sarcoma; MSI-H, microsatellite instability-high; MT, mutant type; NRAS, neuroblastoma rat sarcoma; OS, overall survival; PFS, progression-free survival; RAS, rat sarcoma; WT, wild type.

References: 1. Patel JN, et al. J Pers Med. 2019;9:3. 2. Fakih M, et al. Oncologist. 2022;27:663-674. 3. Ohishi T, et al. Int J Mol Sci. 2023;24:1702. 4. Peeters M, et al. Eur J Cancer. 2015;51:1704-1713. 5. Biller LH, et al. JAMA. 2021;325:669-685. 6. Cervantes A, et al. Ann Oncol. 2023;34:10-32. 7. Lee JK, et al. Prec Oncol. 2022;6:91.

Patients with RAS mutations, a prevalent driver of metastatic colorectal cancer (mCRC), have failed to benefit from targeted treatment1-3

Prevalence of RAS mutations in mCRC4

Compared to other biomarkers, a real-world study suggests that KRAS G12C mutations may be prognostic for poorer outcomes2,‡

Median OS among patients in the KRAS G12C, KRAS﻿ non-G12C, and overall mCRC cohorts2

Due to a lack of targeted options, specific mutational variants like KRAS G12C may be overlooked in mCRC5,6

Patients with RAS mutations, a prevalent driver of metastatic colorectal cancer (mCRC), have failed to benefit from targeted treatment^1-3

Prevalence of RAS mutations in mCRC⁴

Compared to other biomarkers, a real-world study suggests that KRAS G12C mutations may be prognostic for poorer outcomes^2,‡

Median OS among patients in the KRAS G12C, KRAS non-G12C, and overall mCRC cohorts²

Due to a lack of targeted options, specific mutational variants like KRAS G12C may be overlooked in mCRC^5,6