Human Epidermal Growth Factor Receptor 2 Pan Tumor Indication for Trastuzumab Deruxtecan

In April 2024, the US Food and Drug Administration (FDA) granted approval for trastuzumab deruxtecan (T-DXd) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)–positive (immunohistochemistry [IHC] 3+) solid tumors who have received previous systemic treatment and had no satisfactory alternative treatment options.1 The tissue-agnostic indication for T-DXd has been authorized under accelerated approval on the basis of objective response rate (ORR) and duration of response. This marked only the seventh FDA approval of a drug or a combination of drugs for this indication.2 Other drugs that have been approved with a tissue-agnostic indication include selpercatinib, pembrolizumab, larotrectinib, entrectinib, dostarlimab, and dabrafenib in combination with trametinib.2 Recently, the FDA issued a draft guidance document on Tissue-Agnostic Drug Development in Oncology, where the term tissue-agnostic drug was described as a drug that targets specific molecular alterations across multiple cancer types, classified by organ, tissue, or tumor type.3 If an oncology drug is approved as a tissue-agnostic drug, it can be used to treat multiple types of cancers with a prespecified targeted molecular alteration.