Central nervous system metastases in advanced non-small cell lung cancer: A review of the therapeutic landscape

Michael Weller; Jordi Remon; Stefan Rieken; Philipp Vollmuth; Myung-Ju Ahn; Giuseppe Minniti; Emilie Le Rhun; Manfred Westphal; Priscilla K Brastianos; Ross A Soo; John P Kirkpatrick; Sarah B Goldberg; Katarina Öhrling; Fiona Hegi-Johnson; Lizza E L Hendriks

doi:10.1016/j.ctrv.2024.102807

Central nervous system metastases in advanced non-small cell lung cancer: A review of the therapeutic landscape

Cancer Treat Rev. 2024 Nov:130:102807. doi: 10.1016/j.ctrv.2024.102807. Epub 2024 Aug 2.

Authors

Affiliations

¹ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: [email protected].
² Paris-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, France. Electronic address: [email protected].
³ Department of Radiation Oncology, University Hospital Göttingen (UMG), Göttingen, Germany; Comprehensive Cancer Center Lower Saxony (CCC-N), University Hospital Göttingen (UMG), Göttingen, Germany. Electronic address: [email protected].
⁴ Division for Computational Radiology & Clinical AI, Clinic for Neuroradiology, University Hospital Bonn, Bonn, Germany; Division for Medical Image Computing, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: [email protected].
⁵ Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: [email protected].
⁶ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy. Electronic address: [email protected].
⁷ Departments of Neurosurgery and Neurology, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: [email protected].
⁸ Department of Neurosurgery and Institute for Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: [email protected].
⁹ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
¹⁰ Department of Hematology-Oncology, National University Hospital, Singapore, Singapore. Electronic address: [email protected].
¹¹ Departments of Radiation Oncology and Neurosurgery, Duke University, Durham, NC, USA. Electronic address: [email protected].
¹² Department of Medicine (Medical Oncology), Yale School of Medicine, Yale Cancer Center, New Haven, CT, USA. Electronic address: [email protected].
¹³ Amgen (Europe) GmbH, Rotkreuz, Switzerland. Electronic address: [email protected].
¹⁴ Department of Radiation Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia; Sir Peter MacCallum Department of Clinical Oncology, University of Melbourne, Melbourne, Australia. Electronic address: [email protected].
¹⁵ Department of Respiratory Medicine, Maastricht University Medical Centre, GROW School for Oncology and Reproduction, Maastricht, Netherlands. Electronic address: [email protected].

PMID: 39151281
DOI: 10.1016/j.ctrv.2024.102807

Abstract

Up to 40% of patients with non-small cell lung cancer (NSCLC) develop central nervous system (CNS) metastases. Current treatments for this subgroup of patients with advanced NSCLC include local therapies (surgery, stereotactic radiosurgery, and, less frequently, whole-brain radiotherapy), targeted therapies for oncogene-addicted NSCLC (small molecules, such as tyrosine kinase inhibitors, and antibody-drug conjugates), and immune checkpoint inhibitors (as monotherapy or combination therapy), with multiple new drugs in development. However, confirming the intracranial activity of these treatments has proven to be challenging, given that most lung cancer clinical trials exclude patients with untreated and/or progressing CNS metastases, or do not include prespecified CNS-related endpoints. Here we review progress in the treatment of patients with CNS metastases originating from NSCLC, examining local treatment options, systemic therapies, and multimodal therapeutic strategies. We also consider challenges regarding assessment of treatment response and provide thoughts around future directions for managing CNS disease in patients with advanced NSCLC.

Keywords: CNS metastases; Immune checkpoint inhibitors; Non-small cell lung cancer; Small molecules; Stereotactic radiosurgery; Tyrosine kinase inhibitors.

Publication types

Review

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / pathology
Carcinoma, Non-Small-Cell Lung* / therapy
Central Nervous System Neoplasms* / secondary
Central Nervous System Neoplasms* / therapy
Combined Modality Therapy
Humans
Lung Neoplasms* / pathology
Lung Neoplasms* / therapy