New therapies for brain metastases: an update

Brain metastases occur in nearly 20% of all patients with cancer, with a rising incidence in recent years, partly due to improved systemic therapies that have prolonged survival. Traditionally managed with local approaches such as surgery, whole-brain radiotherapy (WBRT), or stereotactic radiosurgery (SRT), the therapeutic landscape has been significantly transformed by the advent of targeted therapies, immune checkpoint inhibitors, and antibody-drug-conjugates (ADCs).

While symptomatic lesions often require local treatment, asymptomatic or oligosymptomatic brain metastases - especially in molecularly defined subgroups - may benefit from upfront systemic therapy. Significant intracranial efficacy has been demonstrated in nonsmall cell lung cancer (NSCLC) with oncogenic drivers treated with tyrosine kinase inhibitor (TKIs), in HER2-positive breast cancer with TKIs and ADCs, and in melanoma with dual immune checkpoint blockade or BRAF/MEK inhibitors. While these therapies have substantially improved intracranial disease control, the survival outcomes remain suboptimal and the optimal sequencing or combination of systemic therapy and local treatments such as SRT is yet to be defined. Several ongoing trials are exploring these strategies with promising early results, warranting further investigation.

The therapeutic landscape of brain metastases has recently been transformed by the emergence of central nervous system (CNS)-penetrant systemic therapies. These advances underscore the need for updated clinical practice guidelines to optimize the overall management of patients with brain metastases.