Evaluation of the efficacy of regorafenib treatment by location and RAS mutation in metastatic colon cancer

The preferred approach for metastatic colon cancer is conventional chemotherapy and biological agents. Despite these treatments, most patients progress to the metastatic stage. Regorafenib inhibits various angiogenic receptor tyrosine kinases and intracellular signaling kinases. This study aimed to determine whether tumor location affects the response to regorafenib treatment in patients with colon cancer. This was a retrospective study, patients who were followed up and treated with a diagnosis of colon cancer in Adana City Training and Research Hospital Medical Oncology Clinic between January 1, 2017 and January 1, 2022 were reviewed. This study included 74 patients with adenocarcinoma, of whom 47 (63.5%) were male and 27 (36.5%) were female. Of these patients, 31 (41.9%) had left colon cancer, 10 (13.5%) had right colon cancer, and 33 (44.6%) had rectal cancer. Genetic analysis of 63 patients was available. KRAS wild-type and mutant tumors were detected in 31 (49.2%) and 32 (51.8%) patients, respectively. While NRAS wild-type was detected in all patients, no BRAF mutation was detected. According to KRAS mutation analysis, progression-free survival and overall survival of patients with KRAS wild-type and KRAS-mutant were 4.12 ± 0.4 and 3.84 ± 0.4 months (P = .711) and 22.1 ± 3.7 and 9.8 ± 1.5 months (P = .030), respectively. Unlike other studies in the literature, we found that the efficacy of regorafenib treatment in the right and left colon was not different. However, we found that this difference in efficacy was associated with the RAS mutation status rather than right-left colon localization. Treatment efficacy decreased in patients with RAS-mutant tumors. We believe that, rather than the right or left colon location, RAS wild-type or RAS-mutant status should be considered when selecting regorafenib treatment.