Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis

• DOI: 10.4143/crt.2022.1058
• Publication Date: 2022-12-23T05:30:52Z
• Authors: Ting Xu; Xicheng Wang; Ying Xin; Zhenghang Wang; Jifang Gong; Xiaotian Zhang; Yanyan Li; Congcong Ji; Yu Sun; Feilong Zhao; Depei Huang; Yuezong Bai; Jian Li; Lin Shen
• Keywords: Clinical endpoint; Leukopenia

Purpose The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. <i>HER2</i> amplification occurs in approximately 1% to 6% colorectal cancer. In this study, we aimed assess the efficacy and safety trastuzumab combination with chemotherapy HER2-positive metastatic cancer (mCRC).Materials Methods An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed evaluate antitumor activity digestive cancers excluding gastric 2017. Patients from HER2-positive, <i>KRAS/BRAF</i> wild-type, unresectable mCRC were analyzed manuscript. Eligible patients treated (8 mg/kg loading dose then 6 every 3 weeks) irinotecan (120 mg/m<sup>2</sup> days 1 8 weeks). primary endpoint objective response rate.Results Twenty-one enrolled study. Seven (33.3%) achieved res-ponse, 11 (52.4%) had stable disease as their best response. median progression-free survival (PFS) 4.3 months (95% confidence interval, 2.7 5.9). Four 21 (19.0%) grade adverse events, including leukopenia, neutropenia, urinary tract infection, diarrhea. No treatment-related death reported. Exploratory analyses revealed that high tumor tissue copy number associated better PFS. Alterations mitogen-activated protein kinase pathway, gene, phosphoinositide 3-kinase/AKT cell cycle control genes potential drivers resistance mCRC.Conclusion Trastuzumab combined a potentially effective well-tolerated regimen number.