More research is needed to determine the prognostic significance of KRAS G12C mutations in metastatic colorectal cancer (mCRC), according to presentations from the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021.

The KRAS G12C mutation has a cysteine residue for which specific drugs have been developed, but data on this mutation in mCRC are limited. 1 

Some researchers have suggested that patients with KRAS G12C-mutant mCRC are more often male, have more lung and liver metastases, have fewer peritoneal metastases, and have shorter overall survival (OS) than patients with other KRAS-mutant cancers.2

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Two studies presented at the ESMO World Congress on Gastrointestinal Cancer were conducted to provide more information on KRAS G12C mutations in mCRC, but the studies produced conflicting results.

Nordic Cohort: No Prognostic Significance

Emerik Österlund, MD, of Uppsala University in Sweden, presented a combined analysis of the prospective Finnish RAXO study (Clinical trial identification: NCT01531595), its population-based data collection substudy, and the population-based Scandinavian SP/PRCRC cohorts.3

The data encompassed 1441 patients with mCRC, including 91 patients with KRAS G12C mutations and 658 with other KRAS mutations. Also included were 456 patients with RAS– and BRAF-wild-type tumors, 54 patients with NRAS mutations, and 182 with BRAF V600E mutations.

When comparing patients with G12C mutations and patients with other KRAS mutations, there were no significant differences with regard to age, sex, performance status, synchronous vs metachronous presentation, number of metastatic sites, or laboratory values.

Left colon primary tumors were slightly more common in patients with G12C mutations than in those with other KRAS mutations (37% vs 33%). Peritoneal metastasis was slightly less common in patients with G12C mutations (14% vs 18%), as was liver metastasis (65% vs 71%). Lung metastasis was slightly more common in patients with G12C mutations (40% vs 34%). 

The proportion of patients who received systemic therapy was similar between the G12C and other KRAS mutation groups (53% vs 59%), with no differences in the number of lines of therapy or drug exposures. Metastasectomy was slightly more common for patients with G12C mutations (38% vs 28%).

Survival outcomes were slightly better in patients with G12C mutations, but there were no significant differences.

The median progression-free survival (PFS) was 13.1 months for those with G12C mutations and 12.0 months for those with other KRAS mutations. The median OS was 31.5 months and 22.8 months, respectively.

OS results were similar between the groups when patients were analyzed by treatment type (systemic therapy, metastasectomy, or best supportive care).

Taken together, these results suggest there are no significant differences in patient characteristics, treatments provided, and outcomes between patients with G12C mutations and those with other KRAS mutations.