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AbstractBackgroundThe objective of this study was to explore the abilities of atezolizumab plus chemotherapy in preventing brain metastases (BMs) among metastatic non–small cell lung cancer (NSCLC) without initial BMs, as well as the risk factors of BMs.MethodsIndividual patient data from three trials involving first‐line atezolizumab for metastatic NSCLC (IMpower130, IMpower131, and IMpower150) were pooled. Among patients without baseline BMs and without epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) mutations, those receiving atezolizumab + chemotherapy ± bevacizumab were classified as the atezolizumab plus chemotherapy group and those receiving placebo + chemotherapy ± bevacizumab were classified as the chemotherapy group. The cumulative incidences of BM (CI‐BMs) between the two groups were compared. Other factors associated with the CI‐BM were analyzed by Cox regression analyses.ResultsWith a median follow‐up of 17.6 months (range, 0.03–33.64 months), 74 (3.1%) of the 2380 enrolled patients developed BMs, including 50 (3.1%) and 24 (3.0%) in the atezolizumab plus chemotherapy group (n = 1589) and the chemotherapy group (n = 791), respectively. The CI‐BMs at 6, 12, and 24 months were 1.7%, 2.8%, and 3.3%, respectively. After taking competing risk events into account, there was no significant difference in the CI‐BMs between the two groups (p = .888). Nevertheless, the use of bevacizumab and the histology of nonsquamous NSCLC were found to be independently associated with the risk of BMs.ConclusionsIn patients with metastatic EGFR/ALK wild‐type NSCLC without baseline BMs, adding atezolizumab in the first‐line treatment might not reduce the CI‐BM. However, the administration of bevacizumab may reduce the risk of BMs.