Survival Benefit of Metastasectomy in First-line Cetuximab Therapy in Patients with RAS Wild-type Metastatic Colorectal Cancer: a Nationwide Registry

This multicenter study aimed to explore the survival benefit of metastasectomy by first-line cetuximab-based chemotherapy in real-world patients with wild-type metastatic colorectal cancer (mCRC). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and metastasectomy rate. The exploratory endpoint was the optimal treatment cycle for better OS and PFS. Receiver operating characteristic curve with the area under curve (AUC) was used to identify the optimal cut-off cycle for survival outcomes. A total of 758 mCRC patients were enrolled in this study, with a median OS of 35.1 months, median PFS of 14.6 months, and metastasectomy rate of 21.4%. Left-sided mCRC had a significantly higher DCR (88.9% vs. 73.1%, <0.001) and better OS (36.4 vs. 19.6 months, <0.001). There were no significant differences in PFS and metastasectomy rate between left-sided and right-sided mCRC. However, mCRC patients who underwent metastasectomy over the course of treatment had better OS (54.9 vs. 28.6 months, <0.001) and PFS (21.0 vs. 13.1 months, <0.001) than those who did not. Notably, right-sided mCRC who benefited from first-line cetuximab-based chemotherapy to underwent metastasectomy also had favorable outcomes, on a par with left-sided mCRC. The optimal treatment cycle was 14 cycles (AUC: 0.779, <0.001). Patients who received ≥14 cycles had higher metastasectomy rates (27.5% vs. 13.5%, <0.001), favorable OS (42.6 vs. 23.4 months, <0.001) and PFS (18.1 vs. 8.6 months, <0.001), and, importantly, had comparable adverse events compared with patients who received <14 cycles of treatment. Patients who underwent metastasectomy after or during first-line cetuximab therapy have an improved OS in both left-sided and right-sided mCRC. Furthermore, patients receive ≥14 cycles of treatment whenever possible to achieve a higher likelihood of metastasectomy was associated with favorable survival outcomes.