Targeting HER2 in lung cancers: Evolving treatment landscape and drug development strategies Review
| Authors: | Reinhorn, D.; Moskovitz, M.; Tap, W. D.; Li, B. T. |
| Review Title: | Targeting HER2 in lung cancers: Evolving treatment landscape and drug development strategies |
| Abstract: | ERBB2 (HER2) alterations, including mutations, amplifications, and overexpression are emerging therapeutic targets in non–small cell lung cancer (NSCLC). Despite recent advancements, standard first-line therapy remains chemotherapy with or without immunotherapy. Several therapies targeting HER2 are under development and have been evaluated in clinical trials with inconsistent efficacy, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates. A major landmark was recently reached when trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate, became the first Food and Drug Administration (FDA)-approved therapy for pretreated HER2-mutant NSCLC, following the promising efficacy demonstrated in the DESTINY-Lung trials. Furthermore, T-DXd has shown efficacy across various tumor types harboring HER2 alterations in the DESTINY-PanTumor trials, leading to its recent pan-tumor FDA approval for HER2-positive solid tumors, highlighting the potential of tumor-agnostic drug development strategies. In this review, the authors describe the different HER2 alterations and their clinical consequences, including their impact on prognosis and response to standard therapies. They provide an up-to-date overview of the current treatment landscape and add a comprehensive review of pivotal and ongoing clinical trials of HER2-targeted therapies, including tumor-agnostic drug development strategies. © 2025 American Cancer Society. |
| Keywords: | genetics; mutation; review; nonhuman; side effect; solid tumor; metabolism; phase 2 clinical trial; protein kinase inhibitor; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor 2; camptothecin; lung cancer; drug development; tyrosine kinase inhibitors; protein kinase inhibitors; lung tumor; drug combination; targeted therapy; receptor, erbb-2; phase 1 clinical trial; drug therapy; trastuzumab; non-small cell lung cancer; adverse drug reaction; therapy; pharmacokinetics; non small cell lung cancer; molecularly targeted therapy; erbb2 protein, human; antibody conjugate; immunoconjugates; molecular targeted therapy; procedures; first-line treatment; her2 amplification; humans; human; her2 mutation; her2 overexpression; antibody drug conjugate; trastuzumab deruxtecan; antibody–drug conjugate; pan-tumor |
| Journal Title: | Cancer |
| Volume: | 131 |
| Issue: | Suppl. 1 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2025-03-15 |
| Start Page: | e35780 |
| Language: | English |
| DOI: | 10.1002/cncr.35780 |
| PUBMED: | 40171885 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Daniel Reinhorn -- Source: Scopus |
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