Dr Eng on the Implications of a Real-World Study in KRAS G12C–Mutated CRC

“We have 2 drugs approved for patients with previously treated CRC, but we now have trials specific to [patients with] KRAS G12C–mutated disease. [These real-world data] entice me as a provider, [and make me want] to try to obtain these drugs and participate in these clinical trials.”

Cathy Eng, MD, FACP, FASCO, the David H. Johnson Endowed Chair in Surgical and Medical Oncology, coleader of the Gastrointestinal Cancer Research Program, and a professor of medicine in Hematology and Oncology at Vanderbilt-Ingram Cancer Center, discussed the potential clinical significance of findings from a real-world study evaluating the effect of KRAS G12C mutations on outcomes in patients with metastatic colorectal cancer (mCRC) who received chemotherapy with or without bevacizumab (Avastin).

During the 2025 ESMO Gastrointestinal Cancers Congress, Eng presented data from the real-world study which revealed that patients with mCRC harboring a KRAS G12C mutation (n = 304) achieved a median overall survival (OS) of 18.2 months (95% CI, 14.7-20.0) compared with 19.1 months (95% CI, 18.4-19.8) among those with KRAS G12C–unmutated disease (n = 3855). Additionally, the median progression-free survival (PFS) values among patients with KRAS G12C–mutated disease (n = 180) and those with KRAS G12C–unmutated disease (n = 2185) were 7.1 months (95% CI, 5.9-8.5) and 8.9 months (95% CI, 8.4-9.2), respectively.

Eng noted that there are clinical trials available specifically for patients with KRAS G12C–mutated CRC and that the data from this real-world study have encouraged her to seek out these trials for her patients. For patients with newly diagnosed disease, the ongoing phase 3 CodeBreaK 301 trial (NCT06252649), which is evaluating the KRAS G12C inhibitor sotorasib (Lumakras) in combination with panitumumab (Vectibix) and FOLFIRI (folinic acid, fluorouracil, and irinotecan), represents an intriguing option, she added. Knowing that the presence of a KRAS G12C mutation could affect OS and PFS, participation in a clinical trial specific to these patients is a better option compared with standard chemotherapy, she concluded.