The Long-Term and Short-Term Efficacy of Immunotherapy in Non-Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Meta-Analysis

Abstract

BackgroundAlthough immunotherapy has been widely used, there is currently no research comparing immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). This meta-analysis addresses a gap in the comparison of immunotherapy efficacy, including immune checkpoint inhibitors (ICIs), chemotherapy (CT), radiotherapy (RT), and ICI combined CT or RT.MethodsA search of Pubmed, Cochrane, EMBASE, and ClinicalTrial.gov was conducted to identify studies which enrolled NSCLC patients with BM treated with ICIs. The outcomes consisted of intracerebral overall response rate (iORR), intracerebral disease control rate (iDCR), extracranial overall response rate (EORR), distant brain failure (DBF), local control (LC), progression-free survival (PFS), and overall survival (OS).ResultsA total of 3160 participants from 46 trials were included in the final analysis. Patients treated with immunotherapy were associated with a longer PFS (0.48, 95%CI: 0.41-0.56), and a longer OS (0.64, 95%CI: 0.60-0.69) compared with immunotherapy-naive patients. In prospective studies, dual ICI combined CT and ICI combined CT achieved a better OS. The hazard ratio (HR) of dual ICI combined CT versus dual ICI was 0.61, and the HR of ICI combined CT versus ICI monotherapy was 0.58. Moreover, no statistical difference in PFS, OS, EORR, iORR, iDCR, and EDCR was found between patients with ICI monotherapy and ICI combined cranial radiotherapy. Concurrent ICI combined RT was shown to decrease the rate of DBF (OR = 0.15, 95% CI: 0.03-0.73) compared with RT after ICI. Patients treated with WBRT might have an inferior efficacy than those with SRS because the iORR of SRS was 0.75 (0.70, 0.80) and WBRT was 0. Furthermore, no obvious difference in PFS and OS was observed among the three different types of ICI, which targets PD-1, PD-L1, and CTLA-4, respectively.ConclusionsPatients treated with ICI got superior efficacy to those without ICI. Furthermore, dual ICI combined CT and ICI combined CT seemed to be optimal for NSCLC patients with BM. In terms of response and survival, concurrent administration of SRS and ICI led to better outcomes for patients with BMs than non-concurrent or non-SRS.Importance of the StudyIn the new era of immunotherapy, our meta-analysis validated the importance of immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). By comparing the long-term and short-term impacts of various regimens, all immunotherapy treatments had superior efficacy to immunotherapy-naive. At the same time, through pairwise comparison in immunotherapy, our findings can help clinicians to make treatment decisions for NSCLC patients with BMs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=269621, identifier CRD42021269621.

Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy

“…A phase 2 prospective study suggested that a PD-1 inhibitor had CNS efficacy, with an intracranial ORR of 29.7% and PFS of 2.3 months in PD-L1-positive NSCLC patients with untreated BMs (16). Moreover, a series of retrospective studies have reported superior CNS efficacy of ICI therapy compared to ICI-naïve therapy (29)(30)(31). Nevertheless, the vast majority of patients in these studies have wild-type EGFR, and data regarding the intracranial efficacy of ICI therapy in patients with EGFR mutations with BMs are rare.…”

NSCLC Patients Achieving Long-term Progression-free Survival With Docetaxel Plus Ramucirumab: A Retrospective Study

“…There has been no established definition for 'long-term PFS' in anticancer chemotherapy, and it varies by therapy (15)(16)(17)(18). Most of the reported 'long-term PFS' are PFS for first-line chemotherapy, and 'long-term PFS' is rarely used in second-line and subsequent treatments (19).…”

Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis

“…Also, several meta-analyses support that ICI monotherapy is efficacious for metastatic brain tumors [ 7 , 8 ]. However, in the included studies of these meta-analyses, only patients with treatment-naïve metastases were enrolled, and the vast majority of prospective studies excluded patients with symptomatic brain metastases [ 7 , 8 ]. Yet, only 20% of the patients benefited from immunotherapy [ 7 ].…”

“…However, in the included studies of these meta-analyses, only patients with treatment-naïve metastases were enrolled, and the vast majority of prospective studies excluded patients with symptomatic brain metastases [ 7 , 8 ]. Yet, only 20% of the patients benefited from immunotherapy [ 7 ]. The efficacy of ICIs for other patients needs further investigation.…”