Dr Eng on Real-World Outcomes in US Patients With KRAS G12C–Mutated CRC

“In the entire patient population, the [median] OS was 20.2 months, but patients with KRAS G12C–mutated disease it was lower.”

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 findings from a real-world study of the effect of KRAS G12C mutations on outcomes in patients with metastatic colorectal cancer (CRC) who received chemotherapy with or without bevacizumab (Avastin) in the United States (US).

To conduct their study, investigators identified 12,318 patients with metastatic CRC using the Flatiron Foundation Medicine Clinico-Genomic database. Of these specimens, 455 had KRAS G12C–mutated disease and 5551 had KRAS G12C wild-type disease, Eng detailed. The presence of KRAS G12C was slightly higher than investigators had anticipated, she noted. The study authors shared that the baseline patient characteristics were similar across the 3 cohorts.

Findings from the analysis, which were presented during the 2025 ESMO Gastrointestinal Cancers Congress, showed that the median overall survival (OS) in the overall patient population (n = 8564) was 20.2 months (95% CI, 19.5-20.9), Eng said. Patients with disease harboring a KRAS G12C mutation (n = 304) experienced a median OS of 18.2 months (95% CI, 14.7-20.0) and those without a KRAS G12C mutation (n = 3855) had a median OS of 19.1 months (95% CI, 18.4-19.8), she added.

Eng noted that the presence of a KRAS G12C mutation was also associated with numerically lower median progression-free survival (PFS) vs KRAS G12C wild-type disease. The median real-world PFS in the overall population (n = 4905) was 9.0 months (95% CI, 8.8-9.3). Among patients with KRAS G12C–mutated disease (n = 180), the median real-world PFS was 7.1 months (95% CI, 5.9-8.5). The median real-world PFS in the KRAS G12C wild-type cohort (n = 2185) was 8.9 months (95% CI, 8.4-9.2).