Management of Brain Metastases: A Review of Novel Therapies

Abstract

Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery. The next generation of local strategies includes laser interstitial thermal therapy, magnetic hyperthermic therapy, post-resection brachytherapy, and focused ultrasound. New targeted therapies and immunotherapies with documented intracranial activity have transformed clinical outcomes. Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective “rearranged during transfection” inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody–drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.

The effectiveness of combined resection and radiotherapy for primary pineal malignant melanoma: a systematic review

“…Nevertheless, this finding suggests that some PPMM patients may respond well to BRAF-targeted therapy ( 25 ). Immunotherapy is mainly used to treat patients with multiple melanoma brain metastases, with drugs like ipilimumab and pembrolizumab shown to be effective ( 37 ). Famoso et al reported a case of a PPMM with positive PD-L1 expression.…”

Prognostic Factors and Impact of Therapeutic Intervention in Patients With Brain Metastases at the Initial Presentation

“…WBRT that spares the hippocampus, which affects cognitive function, through the use of intensity-modulated radiation therapy and other modalities, has become the treatment of choice [26]. However, some clinical scenarios still require classical 3DCRT, such as in cases with a short prognosis where the primary tumor or intracranial lesions have become uncontrollable due to lack of response to chemotherapy [27], or when the neurological findings due to BMs are urgent. One of the significant findings of this study is that WBRT using older 3DCRT technology remains a viable option for treating BMs at the initial diagnosis.…”