Abstract
Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.
Highlights
The development of intracranial metastatic disease (IMD) is a frequent and serious complication of cancer, affecting nearly 30% of cancer patients [1]
The development of small molecule or antibody-based agents to target these molecular drivers of cancer and their associated signalling pathways has revolutionized the treatment of patients with HER2-positive breast cancer, epidermal growth factor receptor (EGFR)-mutant or anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), and BRAF-mutant melanoma (Table 1)
Furmonertinib exhibited good treatment efficacy in a phase I/II trial involving 17 EGFR-mutant NSCLC patients with brain metastases (BrM) [132]. These findings were replicated in a phase IIb trial involving 105 EGFR-mutant NSCLC patients with BrM: In 29 patients with one or more measurable BrM, treatment with alflutinib achieved an intracranial ORR (iORR) of 66%, while among the 87 patients in the complete analysis dataset, iORR was 34% and median progression-free survival (PFS) was 11.6 months
Summary
The development of intracranial metastatic disease (IMD) is a frequent and serious complication of cancer, affecting nearly 30% of cancer patients [1]. The incidence of IMD is expected to increase as our population ages and as advancements in primary cancer therapy result in longer disease survival [1]. Among patients with brain metastases (BrM), lung cancer, breast cancer, and melanoma account for nearly 60%, 11%, and 6% of all primary cancers in some studies [2]. Several algorithms have since been created to identify asymptomatic, high-risk patients who would benefit from MRI screening at the time of their primary cancer diagnosis [3]. Recent data have supported a role for systemic targeted therapies and immunotherapies in the treatment of select patients with IMD, including but not limited to those with non-small cell lung cancer (NSCLC), breast cancer, and malignant melanoma [12, 13]. We outline and describe recent and current efforts to improve outcomes in patients with IMD of the brain through novel therapeutics, improved surveillance, and prevention
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