Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

Abstract

Immune checkpoint inhibitors have revolutionized the treatment landscape for patients with non-small cell lung cancers. Existing treatment paradigms for brain metastases in lung cancer patients leave patients with adverse neurocognitive function, poor quality of life, and dismal prognosis, thus highlighting the need to develop more effective systemic therapies. Although data are limited, emerging knowledge suggests promising activity and safety of immune checkpoint inhibitors in brain metastases in non-small cell lung cancer patients. This review aims to summarize the current data, highlight the challenges of incorporating immune checkpoint inhibitors in treating these patients, and identify areas for future research.

KRT8 Serves as a Novel Biomarker for LUAD and Promotes Metastasis and EMT via NF-κB Signaling

“…For cancer cells to occur at distant sites, these may grow into clinically relevant macrometastases ( 22 , 23 ). For lung cancer, almost a third of patients develop brain metastasis at some point during their disease course ( 24 ). As reported, KRT8 plays a key role in gastric cancer ( 9 ) and renal cancer ( 13 ) by regulating cell migration and invasion.…”

Impact of Brain Metastases on Treatment Patterns and Outcomes With First-Line Durvalumab Plus Platinum-Etoposide in Extensive-Stage SCLC (CASPIAN): A Brief Report

“…5,15 In addition, they are consistent with prospective, albeit limited, data from recent studies of immune checkpoint inhibitors in patients with NSCLC having brain metastases, and supported by preclinical data challenging the notion that the brain is an immuneprivileged site. [16][17][18][19] Furthermore, the 3-year OS data from the CASPIAN study continue to exhibit similar benefits with durvalumab plus EP in patients with or without baseline brain metastases. 10 There are, however, potential limitations of these analyses, including the small subgroups, which preclude, for example, an assessment of the effects of durvalumab in the presence or absence of previous or concurrent brain radiotherapy as there are too few patients who received either.…”

Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis

“…Bevacizumab administration and surgery may lessen the impact of steroids on both the IC and EC efficacy of ICI in carefully selected patients. 96…”

“…The management of radiation necrosis in ICI‐treated patients constitutes another challenging issue because of the high doses of steroids that are required in this case. Bevacizumab administration and surgery may lessen the impact of steroids on both the IC and EC efficacy of ICI in carefully selected patients 96 …”