Discrepant Intracranial and Extracranial Responses to Tarlatamab in Relapsed Small‐Cell Lung Cancer With Untreated Brain Metastases: A Case Report

ABSTRACT Small‐cell lung cancer (SCLC) has a poor prognosis, and the efficacy of tarlatamab for untreated brain metastases remains unclear. We report a case demonstrating a discrepant response between extracranial and intracranial lesions after tarlatamab treatment. A 72‐year‐old man with extensive‐stage SCLC experienced disease progression after multiple prior treatments and subsequently developed untreated brain metastases. Tarlatamab was initiated because of rapidly progressive extracranial disease. After one cycle, marked shrinkage of extracranial lesions and decreases in tumour markers were observed. By contrast, brain magnetic resonance imaging showed progression of intracranial metastases. Whole‐brain irradiation was subsequently performed, and tarlatamab treatment was continued. This case highlights a clear discordance between intracranial and extracranial responses to tarlatamab. Possible explanations include limited drug penetration across an intact blood–brain barrier and biological heterogeneity between metastatic sites. Careful neurological assessment and early brain imaging should be considered when using tarlatamab in patients with untreated brain metastases.