Navigate Towards the Immunotherapy Era: Value of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Brain Metastases

Abstract

Brain metastases (BMs) in non-small-cell lung cancer (NSCLC) patients are associated with significant morbidity and poor prognosis. Immune checkpoint inhibitors (ICIs) have resulted in a paradigm shift in the management of advanced NSCLC. However, the value of ICIs in NSCLC patients with BMs remains unclear because patients with BMs are routinely excluded in numerous prospective trials on ICIs. Here, starting from the mechanisms of ICIs for BMs, we will reveal the value of ICIs by reviewing the efficacy and adverse effects of ICIs monotherapy as well as promising combination strategies, such as combinations with chemotherapy, radiotherapy, and anti-angiogenic drugs, etc. In addition, the methods of patient selection and response assessment will be summarized to assist clinical practice and further studies.

Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy

“…The estimated PFS rate was 59% (95% CI [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] in the Sintilimab-IBI305-CT group versus 30% (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) in the CT alone group at 6 months, and 28% versus 12% (7-20) at 12 months. The prespecified subgroup analysis showed that the HR for PFS favored patients receiving Sintilimab-IBI305-CT over those receiving CT alone across most subgroups, including patients with BM.…”

“…It is commonly believed that anti-angiogenic agents limit tumors growth by inhibiting the unregular vasculature of tumors. However, different studies have demonstrated that low dose of antiangiogenic drugs could induce the normalization of abnormal tumor vascularization, decreasing hypoxia induced by tumor and increasing accessibility for immune cells (65,66). Another approach in the management of advanced CNMP is combinations with antiangiogenic drugs.…”

Immunotherapy in NSCLC Patients with Brain Metastases

“…Patients with BMs are mostly underrepresented in clinical trials [74] and prospective data regarding their treatment are limited to clinically selected subgroup of patients with asymptomatic and stable BMs, not requiring significative corticosteroid therapy. To provide real-world evidence on the outcome of these patients, an international real-world study evaluated outcomes of patients with NSCLC treated with first-line anti-PD-1 or anti-PD-L1 monotherapy, also including those with active BMs (39.2%), symptomatic BMs (14.3%), or receiving steroids (27.4%) [75].…”

Choice of radiotherapy modality for the combined treatment of non-small cell lung cancer with brain metastases: whole-brain radiation therapy with simultaneous integrated boost or stereotactic radiosurgery

“…The conventional view is that anti-tumor drugs are subject to the central nervous system (CNS) barrier (blood-brain barrier/bloodtumor barrier). However, Several studies have shown that novel drugs, such as three generations-targeted drugs and immune checkpoint inhibitors (ICIs), can achieve effective therapeutic concentrations in the CNS (2,3). In addition, Radiation has synergistic effects with the drugs mentioned above (4)(5)(6)(7)(8)(9).…”