CNS activity of trastuzumab deruxtecan in HER2-expressing non-small-cell lung cancer

• Published in: The lancet oncology 2024-07, Vol.25 (7), p.e282-e282
• Main Authors: Lazaratos, Anna-Maria, Petrecca, Kevin, Guiot, Marie-Christine, Jerzak, Katarzyna J, Dankner, Matthew
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Immunological - therapeutic use; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cerebrospinal fluid; Clinical trials; ErbB-2 protein; Female; Humans; Immunoconjugates - therapeutic use; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Meninges; Metastases; Metastasis; Molecular modelling; Non-small cell lung carcinoma; Patients; Receptor, ErbB-2 - metabolism; Response rates; Small cell lung carcinoma; Trastuzumab; Trastuzumab - therapeutic use; Tumors
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(24)00261-4

The molecular mechanism underlying the CNS activity of trastuzumab deruxtecan remains elusive and is an area of active investigation, as it is known that trastuzumab administered intravenously reaches the cerebrospinal fluid in the CNS at only 1–10% of its serum concentration.5 Nonetheless, trastuzumab deruxtecan has demonstrated intracranial objective response rates of up to 73% in patients with metastatic HER2-positive breast cancer and active CNS metastases in the TUXEDO trial.4 Patients with HER2-expressing metastatic NSCLC with active CNS disease represent a distinct population primed to derive benefit from trastuzumab deruxtecan. Given the relative rarity of patients with HER2-expressing metastatic NSCLC with active brain or leptomeningeal metastases, the engagement of international clinical trial networks might improve feasibility of such approaches. KJJ has been a consultant, speaker, or advisory board member for Amgen, AstraZeneca, Apo Biologix, Daiichi Sankyo, Eli Lilly, Esai, Genomic Health, Gilead Sciences, Knight Therapeutics, Merck, Myriad Genetics, Organon, Seagen (now Pfizer), Roche, Novartis, and Viatris; has received research funding from AstraZeneca, Eli Lilly, and Seagen (now Pfizer); has received support for attending meetings or travel from AstraZeneca and Daiichi Sankyo; has a patent regarding compounds for treating cancer and methods of use thereof (US patent 10 576 056; Europe patent 3 393 466); and has received drug supply from Viatris for an investigator initiated clinical trial.