MET-11 Recent advances in targeted therapies and immunotherapy for metastatic brain tumors

This presentation outlines CQ2 of Chapter 2 from the forthcoming updated version of the Clinical Practice Guidelines for Brain Tumors, edited by the Society. These guidelines discuss chemotherapy and other drug therapies for metastatic brain tumors in adult patients. First, there is no noteworthy change in the principle of prioritizing local treatment of symptomatic metastatic brain tumors or those that require local treatment in the near future. However, with recent advances in molecular-targeted drugs and/or immune checkpoint inhibitors, many physicians now consider starting systemic treatment prior to local treatment of brain metastases, even in patients with solid tumors that were once considered insensitive to chemotherapy, given that their symptoms are well-controlled and do not require urgent treatment. In the treatment of non-small cell lung cancer (NSCLC), the molecular subtypes of metastatic brain tumors with EGFR mutations and ALK fusion genes have yielded favorable responses to molecular-targeted drugs. Because small molecule drugs are well delivered to the central nervous system, systemic drug therapy with such targeted drugs is commonly selected for patients with untreated metastatic brain tumors. A recent phase II trial has shown the effectiveness of anti-PD-1 antibody pembrolizumab monotherapy for metastatic brain tumors from NSCLC. Because untreated metastatic brain tumors from renal cell carcinoma are prone to bleeding, local treatment of brain metastases should be prioritized before systemic treatment, even if the patient is asymptomatic. Regardless of BRAF mutation status, immune checkpoint inhibitors alone or in combination (nivolumab and ipilimumab) are effective against malignant melanoma with brain metastases; moreover, a combined treatment with BRAF and MEK inhibitors is effective against BRAF mutation-positive malignant melanoma with brain metastases. A novel HER2 inhibitor, tucatinib (unapproved), is expected to be effective against metastatic brain tumors from HER2-positive breast cancer.