Efficacy of continued cetuximab for unresectable metastatic colorectal cancer after disease progression during first-line cetuximab-based chemotherapy: a retrospective cohort study

// Qingyang Feng 1, * , Ye Wei 1, * , Li Ren 1, * , Peng Zheng 1, * , Yiyi Yu 2 , Qinghai Ye 3 , Jianyong Ding 4 , Jingwen Chen 1 , Wenju Chang 1 , Yunshi Zhong 1 , Dexiang Zhu 1 , Qi Lin 1 , Liangliang Yang 1 , Xinyu Qin 1 , Jianmin Xu 1 1 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China 2 Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China 3 Department of Liver Surgery, Zhongshan Hospital, Fudan University, Shanghai, China 4 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence to: Jianmin Xu, e-mail: xujmin@aliyun.com Keywords: colorectal cancer, metastasis, cetuximab, cross-line treatment, early tumor shrinkage Received: September 11, 2015 Accepted: January 23, 2016 Published: February 04, 2016 ABSTRACT This study assessed second-line continued use of cetuximab for treatment of unresectable metastatic colorectal cancer (mCRC) after disease progression during first-line cetuximab-based therapy. Consecutive patients with wild-type KRAS exon 2 and unresectable mCRC were retrospectively enrolled after disease progression during first-line cetuximab-based chemotherapy. Second-line continued cetuximab plus changed chemotherapy (cetuximab continuation group, n = 102) was compared with changed chemotherapy only (chemotherapy only group, n = 96) with respect to treatment efficacy and safety endpoints. NRAS and other KRAS genotypes were also detected as a post hoc analysis. The cetuximab continuation group showed better progression-free survival (median, 6.3 vs. 4.5 months, P = 0.004), overall survival (median, 17.3 vs. 14.0 months, P < 0.001) and disease control rate (70.6% vs. 53.1%, P = 0.011), and a potentially better overall response rate (18.6% vs. 9.4%, P = 0.062) than the chemotherapy only group. These benefits were seen mainly in patients with all RAS wild-type and exhibiting first-line early tumor shrinkage (ETS). For patients with other RAS mutations or who did not achieve first-line ETS, there was no difference between the two groups. These findings suggest that for patients with all RAS wild-type and unresectable mCRC who had disease progression during first-line cetuximab-based treatment, second-line continued cetuximab is effective. Moreover, ETS during first-line cetuximab-based treatment may be predictive of the efficacy of second-line continued cetuximab.