KRAS p.G12C mutated-targeted treatments in metastatic colorectal cancer: a systematic review and meta-analysis

Abstract

Background Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The presence of the KRAS G12C mutation in patients with CRC is associated with poor responses to standard therapies and worse outcomes. This study systematically reviewed and analyzed the existing evidence on the efficacy of KRAS G12C inhibitors.

Methods PubMed, Scopus, and ISI Web of Knowledge were searched, along with conference proceedings, posters, and major oncology journals. Eligibility criteria included clinical trials involving adult patients with KRAS G12C-mutant CRC. Data on treatment outcomes, study design, and patient demographics were extracted and analyzed using a random-effects model, with heterogeneity assessed via I2 statistics.

Results Seventeen trials, comprising 663 patients with KRAS G12C-mutant metastatic CRC, were included. Monotherapy with KRAS G12C inhibitors demonstrated an objective response rate of 23%, while combination therapies with agents such as cetuximab and panitumumab showed a higher response rate of 43%. Stable disease rates were also higher in monotherapy (62%) compared to combination therapy (44%). The highest disease control rates were observed with combination therapies (96%). The overall progressive disease rate was lower with combination therapies (1%) than with monotherapies (10%).

Conclusions The results indicate that KRAS G12C inhibitors, particularly in combination with other agents, show promising efficacy in treating metastatic CRC. High heterogeneity across studies suggests variability due to small sample sizes and early-phase trial designs. While preliminary data are promising, further large-scale phase III trials are essential to establish these inhibitors as a standard treatment for KRAS G12C-mutant CRC.

Keywords Colorectal cancer, KRAS G12C mutation, targeted therapy, KRAS G12C inhibitors, meta-analysis

Ann Gastroenterol 2026; 39 (1): 88-98