The detailed search strategy is shown in Supplementary File, Table S2. The reference lists of relevant studies were checked for additional articles. Abstracts of recent international scientific meetings, including the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and World Conference on Lung Cancer (WCLC), were also inspected. A systematic literature search of PubMed, Embase, Cochrane Library, and Web of Science up to November 10, 2020, was performed by two authors (LD and JQ) independently. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria ( 22) ( Supplementary File, Table S1). Materials And Methods Literature Search Strategy In addition, differences in survival benefit from ICIs between patients with and without asymptomatic and/or treated BMs were also evaluated. In light of this important issue, we conducted a meta-analysis to assess the efficacy of ICIs relative to CT in NSCLC patients with asymptomatic and/or treated BMs. Whether the presence of asymptomatic and/or treated BMs can affect the efficacy of ICIs remains uncertain. To date, no randomized-controlled trial (RCT) has specifically addressed the role of ICIs in NSCLC patients with BMs. Conversely, CheckMate-227 ( 11, 12), -9LA ( 13), and a pooled analysis of KEYNOTE-021 and -189 and -407 trials ( 21) showed that ICIs significantly improved survival compared with that in CT. In CheckMate-057 ( 9), -078 ( 10), and a pooled analysis of KEYNOTE-010 and -024 and -042 trials ( 20), patients with baseline asymptomatic or treated BMs had similar OS with ICIs or chemotherapy (CT). Some recent RCTs ( 3– 19) have included a small number of patients with asymptomatic and/or treated BMs but with inconsistent results. However, the majority of ICIs trials systematically excluded patients with untreated/unstable BMs. Recently, immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape of metastatic NSCLC patients lacking EGFR or ALK alteration. However, for patients without these genetic aberrations, there are few satisfactory systemic treatment options. Currently, tyrosine kinase inhibitors (TKIs), especially third-generation TKIs, such as osimertinib and alectinib, have been recommended for epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations in NSCLC patients with BMs ( 2). Patients with BMs were likely to obtain more OS benefit from ICI combination therapy than that from monotherapy.īrain metastases (BMs) are a common complication of advanced lung cancer with poor prognosis, occurring in 20% to 40% of patients with non-small cell lung cancer (NSCLC) ( 1). 0.76, P interaction = 0.27).Ĭonclusion: There was no compelling statistical evidence that the efficacy of ICIs in metastatic NSCLC was modified by the presence of asymptomatic and/or treated BMs. 0.81, P interaction = 0.005) but not in patients without BMs (HR, 0.71 vs. Superior OS benefit from ICI combination therapy than that in monotherapy was observed in patients with BMs (HR, 0.49 vs. Subgroup analyses revealed that either ICI monotherapy or combination therapy significantly improved OS and PFS compared with those in chemotherapy both for patients with and without BMs. ICIs were associated with longer OS and PFS than those in chemotherapy either in patients with (hazard ratio, 0.65 95% confidence interval, 0.51–0.82 and HR, 0.60 95% CI, 0.45–0.79) or without BMs (HR, 0.74 95% CI, 0.70–0.78 and HR, 0.70 95% CI, 0.57–0.86) no significant difference in the pooled HRs for OS (P interaction = 0.29) and PFS (P interaction = 0.37) was observed between the two patient populations. Results: Seventeen articles reporting 15 RCTs with 10,358 patients (1,199 with and 9,159 without BMs) were eligible. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Patients and Methods: PubMed, Embase, Cochrane Library, Web of Science, and recent meetings were searched for randomized controlled trials (RCTs). 3Department of Radiation Oncology, Shenyang Chest Hospital, Shenyang, Chinaīackground: To assess the effect of asymptomatic and/or treated brain metastases (BMs) on the efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC).2Department of Radiation Oncology, Anshan Cancer Hospital, Anshan, China.1Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.Sihan Li 1†, Hongwei Zhang 1†, Tingting Liu 2, Jun Chen 3 and Jun Dang 1*
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