Treatment patterns are generally similar for patients with metastatic colorectal cancer (mCRC), whether or not they have KRAS p.G12C mutations, according to a real-world study published in The Oncologist

The data also showed numerically shorter overall survival (OS) and real-world progression-free survival (rwPFS) among patients with KRAS p.G12C mutations.

“These patients appear to have poor treatment outcomes that are worse than those in patients without this mutation or in patients with KRAS non-p.G12C mutations, suggesting prognostic implications and an unmet medical need in this population,” the researchers wrote. 


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For this study, the researchers examined clinicopathologic characteristics, treatment patterns, OS, and rwPFS in patients with mCRC diagnosed between January 1, 2011, and March 31, 2020. The patients were enrolled in the US-based Flatiron Health-Foundation Medicine clinical genomic database.

The study included 6477 patients — 238 with KRAS p.G12C mutations, 2947 with other KRAS mutations, and 2249 with wild-type RAS/BRAF. Baseline characteristics were generally similar across the cohorts.

Most patients had metastatic disease at diagnosis, including 57.7% of the entire cohort, 56.7% with KRAS G12C, 58.0% with KRAS non-G12C, and 57.4% with wild-type RAS/BRAF

Treatment Patterns

Treatment patterns were generally comparable across the cohorts. Specifically, a majority of patients in all cohorts (54% to 60%) received oxaliplatin and fluoropyrimidine, with or without antiangiogenic therapy, as first-line treatment. 

Few patients received fluorouracil or capecitabine monotherapy, with or without antiangiogenic therapy, in any line of treatment.

Second-line treatment was most often irinotecan and fluoropyrimidine, with or without antiangiogenic therapy, for the overall cohort and for the patients with KRAS mutations. However, patients in the wild-type RAS/BRAF cohort were more likely to receive “other” second-line therapies, which included a range of regimens.

Survival Outcomes and Implications

The median OS after first-line therapy was 16.1 months for the KRAS G12C cohort, 18.3 months for the KRAS non-G12C cohort, 23.4 months for the wild-type RAS/BRAF cohort, and 19.2 months for the overall cohort.

The median rwPFS after first-line therapy was 7.4 months for the KRAS G12C cohort, 9.0 months for the KRAS non-G12C cohort, 10.6 months for the wild-type RAS/BRAF cohort, and 9.2 months for the overall cohort. 

“This is the largest retrospective study to date to provide real-world evidence comprehensively characterizing and contextualizing the natural disease history of mCRC patients with KRAS p.G12C mutations and other KRAS mutations,” the researchers wrote. 

They did note that the median age in the current study was 60 years for the overall cohort, which is slightly younger than the median age reported in other studies (roughly 65 years). This may reflect patients coming from community settings and the increasing incidence of CRC in younger adults and declining incidence in older adults, according to the researchers. 

The team also acknowledged that these findings may not be generalizable to all patients with mCRC, specifically patients outside the United States, those treated at academic centers, and those who either did not undergo genomic sequencing or were sequenced by different methodologies.

Disclosures: This research was supported by Amgen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Fakih M, Tu H, Hsu H, et al. Real-world study of characteristics and treatment outcomes among patients with KRAS p.G12C-mutated or other KRAS mutated metastatic colorectal cancer. Oncologist. Published online April 26, 2022. doi:10.1093/oncolo/oyac077