Survival benefit of metastasectomy in first-line cetuximab therapy in patients with RAS wild-type metastatic colorectal cancer: a nationwide registry

Chou-Chen Chen; Shih-Ching Chang; Yu-Yao Chang; Bo-Wen Lin; Hong-Hwa Chen; Yao-Yu Hsieh; Hung-Chih Hsu; Meng-Che Hsieh; Tao-Wei Ke; Feng-Che Kuan; Chih-Chien Wu; Wei-Chen Lu; Yu-Li Su; Yi-Hsin Liang; Joe-Bin Chen; Hsuan-Yuan Huang; Hsiang-Lin Tsai; Jaw-Yuan Wang

Survival benefit of metastasectomy in first-line cetuximab therapy in patients with RAS wild-type metastatic colorectal cancer: a nationwide registry

Am J Cancer Res. 2023 Dec 15;13(12):6333-6345. eCollection 2023.

Authors

Chou-Chen Chen¹, Shih-Ching Chang², Yu-Yao Chang^{3

4}, Bo-Wen Lin⁵, Hong-Hwa Chen⁶, Yao-Yu Hsieh^{7

8}, Hung-Chih Hsu^{9

10}, Meng-Che Hsieh¹¹, Tao-Wei Ke¹², Feng-Che Kuan¹³, Chih-Chien Wu^{14

15}, Wei-Chen Lu¹⁶, Yu-Li Su¹⁷, Yi-Hsin Liang¹⁸, Joe-Bin Chen¹⁹, Hsuan-Yuan Huang³, Hsiang-Lin Tsai^{20

21}, Jaw-Yuan Wang^{20

21

22

23

24}

Affiliations

¹ Department of Surgery, Taichung Veterans General Hospital Taichung, Taiwan.
² Division of Colon and Rectal Surgery, Department of Surgery, Veterans General Hospital Taipei, Taiwan.
³ Department of Colorectal Surgery, Changhua Christian Hospital Changhua, Taiwan.
⁴ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University Taichung, Taiwan.
⁵ Division of Colon and Rectal Surgery, Department of Surgery, National Cheng Kung University Hospital Tainan, Taiwan.
⁶ Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital Kaohsiung, Taiwan.
⁷ Division of Hematology and Oncology, Shuang Ho Hospital, Taipei Medical University New Taipei City, Taiwan.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan.
⁹ Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou Taoyuan, Taiwan.
¹⁰ College of Medicine, Chang Gung University Taoyuan, Taiwan.
¹¹ Division of Hematology Oncology, Department of Internal Medicine, E-Da Hospital, I-Shou University Kaohsiung, Taiwan.
¹² Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital Taichung, Taiwan.
¹³ Department of Hematology and Oncology, Chang Gung Memorial Hospital Chiayi, Taiwan.
¹⁴ Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital Kaohsiung, Taiwan.
¹⁵ School of Medicine, National Yang Ming Chiao Tung University Taipei, Taiwan.
¹⁶ Department of Oncology, National Taiwan University Hospital Yunlin Branch Yunlin, Taiwan.
¹⁷ Division of Hematology Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung, Taiwan.
¹⁸ Department of Oncology, National Taiwan University Hospital Taipei, Taiwan.
¹⁹ Department of Surgery, Chung Shan Medical University Hospital Taichung, Taiwan.
²⁰ Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan.
²¹ Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
²² Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
²³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
²⁴ Center for Cancer Research, Kaohsiung Medical University Kaohsiung, Taiwan.

PMID: 38187069
PMCID: PMC10767339

Abstract

This multicenter study aimed to explore the survival benefit of metastasectomy by first-line cetuximab-based chemotherapy in real-world patients with RAS 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%, P<0.001) and better OS (36.4 vs. 19.6 months, P<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, P<0.001) and PFS (21.0 vs. 13.1 months, P<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, P<0.001). Patients who received ≥14 cycles had higher metastasectomy rates (27.5% vs. 13.5%, P<0.001), favorable OS (42.6 vs. 23.4 months, P<0.001) and PFS (18.1 vs. 8.6 months, P<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.

Keywords: RAS wild-type metastatic colorectal cancer; cetuximab; metastasectomy; optimal treatment cycle; overall survival; progression-free survival.