Background: Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality with limited precision strategies. The human epidermal growth factor receptor (HER2) is amplified in 5% of patients with metastatic CRC. Therapeutic studies have demonstrated activity of HER2 targeting regimens in the late-line treatment setting though little characterization has been done in the setting of not having prior anti-epidermal growth factor receptor antibody therapy or in the first-line treatment setting.

Methods: Patient with metastatic colorectal cancer underwent next-generation sequencing (NGS) panel testing by Strata Oncology through the University of Wisconsin Precision Medicine Molecular Tumor Board. Patients were treated per multi-disciplinary recommendation across multiple lines of therapy and tracked by prospective registry (IRB#UW15068). HER2 copy numbers >/= 10 were used to determine amplification. A subset of patients with HER2-amplified CRC were treated with single agent trastuzumab.

Results: HER2 amplifications were identified in 4 of 78 cases of metastatic CRC (5.1%). All biopsies were performed prior to exposure to anti-epidermal growth factor receptor inhibitors. Median estimated copy number (CN) was 55.5 [range 13-178]. There was no concurrent alterations in extended RAS, BRAF, PIK3CA, AKT or MTOR. All cases included concurrent mutations in TP53 at R175H (2), C135W, or C135F. Single agent trastuzumab was administered to two patients at standard dosing (trastuzumab 8mg/kg intravenous day 1 cycle 1 followed by 6 mg/kg intravenous day 1 cycle 2+ on a 21 day cycle). One patient was treated in the treatment refractory setting. They had resolution of bowel obstructive symptoms and a minor response on imaging. Additionally, a patient with a HER2 amplification (CN 178) was treated in the first-line setting with single agent trastuzumab. The patient had grade 1 fever with the first cycle and no other treatment related adverse events thereafter. The patient’s CEA decreased from 7,506 to 2,525 ng/mL with the first cycle of therapy and overall reduced to 6.5 ng/mL after 12 cycles of therapy. The patient has had a partial response per RECIST v1.1 response criteria with a reduction of cross-sectional diameter of their disease by 60%. The patient currently continues on this therapy without evidence of disease progression.

Conclusions: HER2 amplified colorectal cancers are an important subtype of colorectal cancer. Here we describe the potential benefit of HER2 targeting with single agent trastuzumab and even demonstrate single agent activity in the first-line setting. Further studies should be done to further characterize the benefit of this low toxicity treatment option for patients with metastatic HER2 amplified colorectal cancer.

Citation Format: Jeremy Kratz, Nataliya Uboha, Kayla Lemmon, Hannah Houtler, Mark Burkard, Dustin Deming. Durable response to first-line Trastuzumab in HER2 amplified colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1414.