{
  "abstract": "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. 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. 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology, Dalian Friendship Hospital, Dalian, China."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dongyan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yujun Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d9jxfanje9xcg.bib",
  "cited_by": 0,
  "doi": "10.21037/jgo-2026-1142",
  "fulltext_url": "https://europepmc.org/articles/PMC13740585",
  "id": "d9jxfanje9xcg",
  "issns": [
    "2078-6891",
    "2219-679X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42996595",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Colorectal Cancer Treatments and Studies"
    ]
  ],
  "openalex": "W7224001596",
  "pdf_url": "https://europepmc.org/articles/PMC13740585?pdf=render",
  "pmcid": "PMC13740585",
  "pmid": "42996595",
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d9jxfanje9xcg.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42996595",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996595"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Colorectal Cancer Treatments and Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Trastuzumab rezetecan (SHR-A1811) for the treatment of HER2-positive advanced colorectal cancer: a report of two cases.",
  "title_text": "Trastuzumab rezetecan (SHR-A1811) for the treatment of HER2-positive advanced colorectal cancer: a report of two cases.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/d9jxfanje9xcg",
  "venue": "Journal of gastrointestinal oncology",
  "versions": []
}