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Brain metastases (BMs) occur in approximately 10%\u201350% of patients with NSCLC harboring rare genetic variants. The recent advent of small\u2010molecule tyrosine kinase inhibitors and macromolecular antibody\u2013drug conjugates (ADCs) has conferred marked survival benefits to patients with NSCLC harboring rare driver alterations. Despite effective brain lesion control for most targeted agents and promising reports of intracranial remission associated with novel ADCs, BM continues to be a major therapeutic challenge. This review discusses the recent advances in the treatment of NSCLC with rare genetic variants and BM, with a particular focus on intracranial efficacy, and explores future perspectives on how best to treat these patients.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35070","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T07:41:41Z","timestamp":1719992501000},"page":"2117-2128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Spotlight on the treatment of non\u2010small cell lung cancer with rare genetic alterations and brain metastasis: Current status and future perspectives"],"prefix":"10.1002","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3691-5796","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oncology, The Second Clinical Medical College Zhejiang Chinese Medical University  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