Cumulative incidence and risk factors of brain metastases in metastatic non–small cell lung cancer without baseline brain metastasis: Pooled analysis of individualized patient data from IMpower130, IMpower131, and IMpower150

Abstract

BackgroundThe 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.

Immunotherapy for metastatic non–small cell lung cancer: Is it really a no‐brainer?

“…It also found that the TME had more differences in the metachronous group than the synchronous group comparing primary lung tumors and brain metastasis. This finding is difficult to corroborate clinically at present given the limited data but could be supportive of the findings of Zhou et al 5 showing that patients receiving atezolizumab do not have a difference in developing brain metastasis from those receiving chemotherapy. However, the number of cases in this meta-analysis is small, and data on postprogression CNS disease were not collected.…”

“…With this background, better understanding of the contribution of immunotherapy with or without additional agents in the management/prevention of CNS metastasis is of significant interest. Zhou et al 5 Abbreviations: HR, hazard ratio; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival.…”

“…Zhou et al's provocative findings highlight the need for further clinical trials to better assess the impact of CPIs on CNS disease (Table 2). 5 There is still much progress to be made in understanding the underlying mechanisms of brain metastasis development in NSCLC, and it is very important to expand research in this area because brain metastasis strongly affects patients' OS. There is evidence of improved survival for patients having oncogene driver mutations with a TKI plus chemotherapy versus a TKI alone.…”

“…In this most recent meta-analysis of a data pool from the pivotal IMpower130, IMpower131, and IMpower150 studies, Zhou et al in this issue of Cancer explore metastatic EGFR and ALK wild-type NSCLC to determine potential preventative factors and risk factors for the development of brain metastasis. 5 More specifically, they aim to answer the question of whether immunotherapy (the anti-PD-L1 [anti-programmed death ligand 1] antibody, atezolizumab in particular) plays a role in preventing brain metastasis.…”

“…The ongoing PRAG-MATICA study comparing pembrolizumab and the anti-VEGFR2 antibody ramucirumab with standard second-line chemotherapy is anticipated to provide relevant information in this context. 30 Although post hoc analysis of previous studies such as the study of Zhou et al 5 may not at present affect practice, it certainly calls us to action for further clinical trials expanding our knowledge of the contribution of different systemic agents to the management and mitigation of the burden of CNS disease in patients with advanced NSCLC. This is indeed a no-brainer!…”