Abstract
BackgroundThe predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low.MethodsPubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups.ResultsA total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52–0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48–0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84–3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69–1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78–1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49–0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable.ConclusionsThe efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.
Highlights
The predictive role of blood-based tumor mutation burden for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate
The efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor therapy in advanced NSCLC patients may be dependent on based tumor mutation burden (bTMB) level
Different PD-1/PD-L1 inhibitors were used in the intervention arm, including 4 trials that used PD-L1 inhibitors as monotherapy, 2 trials that used PD-1 inhibitors plus CT, and 1 trial that used a PD-L1 inhibitor plus a CTLA-4 inhibitor
Summary
The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. The purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low. In the past few years, programmed cell death 1 (PD-1)/ programmed cell death ligand 1(PD-L1) inhibitor therapy has replaced chemotherapy (CT) as the new standard second- or later-line therapy for many tumors. The identification of biomarkers that are adequate to screen patients more likely to experience greater efficacy is necessary. More biomarkers that can be used to screen the population that would benefit from PD-1/PD-L1 inhibitor therapy are urgently needed
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