Trastuzumab rezetecan (SHR-A1811) for the treatment of HER2-positive advanced colorectal cancer: a report of two cases
Year: 2026
Type: article
Abstract: Background: Trastuzumab rezetecan (SHR-A1811) is a novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC). Its activity in HER2-positive advanced colorectal cancer (CRC) has been suggested by a phase I cohort (n=37; objective response rate 40.5%), but real-world experience is lacking. Case Description: We describe two patients with advanced CRC whose tumors were reported as HER2-positive by immunohistochemistry (IHC) score 2+ but were not confirmed by in situ hybridization (ISH)/fluorescence in situ hybridization (FISH) before treatment. Case 1 was a 53-year-old man with RAS/BRAF wild-type sigmoid and left colon adenocarcinoma with liver and peritoneal metastases who had received three prior lines of therapy (>15 cycles of cumulative irinotecan exposure and prior anti-EGFR therapy). He received three cycles of SHR-A1811 200 mg plus bevacizumab (starting June 5, 2026) and developed progressive disease-an enlarging left iliopsoas lesion with worsening abdominal pain, and a rise in carcinoembryonic antigen (CEA) from 157.0 to 253.0 ng/mL. Biopsy of the progressing left psoas lesion was HER2-negative (IHC 0). Case 2 was an 80-year-old man with KRAS G12S-mutant anal mucinous adenocarcinoma, bilateral lung metastases, and baseline interstitial lung changes. He received three cycles of SHR-A1811 200 mg plus bevacizumab, after which bevacizumab was discontinued for bleeding and replaced by tislelizumab for the fourth cycle; FISH was negative (HER2-low). The lung lesions remained stable without worsening of the interstitial lung changes, although CA72-4 rose from 16.27 to 36.38 U/mL. Neither patient experienced grade ≥3 adverse events attributable to SHR-A1811. Conclusions: Neither patient achieved an objective response [one progressive disease, one stable disease (SD)]. Confirmatory testing showed the progressing lesion in Case 1 to be HER2-negative (IHC 0) and Case 2 to be FISH-negative (HER2-low). These observations illustrate that an IHC 2+ result alone does not establish HER2 positivity and may not predict benefit from HER2-directed ADC therapy, supporting confirmatory ISH/FISH testing before treatment selection.
Authors: Dongyan Chen, Yujun Zheng
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224001596