Is there any opportunity for immune checkpoint inhibitor therapy in non-small cell lung cancer patients with brain metastases?

Although brain metastases occur in almost one-third of non-small cell lung cancer (NSCLC) patients, and immune checkpoint inhibitors (ICI) either as monotherapy or combined with chemotherapy are the new standard of care in the first line setting, most trials excluded patients with asymptomatic and/or untreated brain metastases. Brain metastases have a major clinical impact due to the worsening of the patient's prognosis and quality of life. Furthermore, the incidence of brain metastases is increasing in NSCLC patients, due to a longer survival and better imaging techniques. Therefore, brain metastases are increasingly becoming a research topic. Recent clinical data endorses ICI as a therapeutic strategy in this subpopulation of NSCLC patients, although the immune environment in brain metastases is more immune ignorant compared with the microenvironment in the primary tumour or in the extracranial metastases. In this review we summarize the current evidence of ICI strategy in NSCLC patients with brain metastases, including trial and real-life data. We also state that the different tumor microenvironment between brain metastases and primary tumor may explain the discordance on the response rate during treatment with ICI. Last, we focus on future directions, including the role and optimal sequence of cranial irradiation and ICI, prognostic scores, the best response assessment and new imaging techniques.

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2021 Translational Lung Cancer Research. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-343). The focused issue “Immunotherapy in other thoracic malignancies and uncommon populations” was commissioned by the editorial office without any funding or sponsorship. JR served as the unpaid Guest Editor of the focused issue and serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. BB served as the unpaid Guest Editor of the focused issue. LH: none related to current manuscript, outside of current manuscript: research funding Roche, Boehringer Ingelheim, AstraZeneca (all institution), advisory board: Boehringer, BMS, Lilly, Roche, Pfizer, Takeda, MSD (all institution), speaker: MSD, travel/conference reimbursement: Roche, BMS (self); mentorship program with key opinion leaders: funded by AstraZeneca; fees for educational webinars: Quadia (self), interview sessions funded by Roche (institution). JR: none related to current manuscript, outside of current manuscript: advisory: Boehringer-Ingelheim, MSD, Pfizer, BMS, AstraZeneca. Travel: OSE immunotherapeutics, BMS, AstraZeneca. JM: none related to current manuscript, outside of current manuscript: advisory: Boehringer-Ingelheim, MSD, Roche. Travel: Boehringer-Ingelheim, MSD, BMS, AstraZeneca. BB: Sponsored Research at Gustave Roussy Cancer Center Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. The authors have no other conflicts of interest to declare.