Abstract:BackgroundNivolumab improves the survival of advanced non-small cell lung cancer (NSCLC), but a significant number of patients still fail to benefit from this treatment. In this study, we evaluated the efficacy of the time-series behavior of neutrophil-to-lymphocyte ratio (NLR) in a complete blood count from advanced NSCLC patients as a predictive marker of the anticancer effect of nivolumab.MethodsWe performed a retrospective review of medical records and collected data on patients with advanced NSCLC treated… Show more
“…As shown in Figure 2B, the pooled HRs of OS from eight studies 16,18,19,28,30,33,35,36 using random effect model was 1.75(95%CI: 1.33, 2.30), favoring NSCLC patients with low pre-treatment NLR.10.1080/2162402X.2018.1507262-F0002Figure 2.Comparisons of PFS and OS in Nivolumab treated NSCLC patients with different baseline NLR. A, NLR < cutoff value(low NLR) versus NLR≥ cutoff value(high NLR) for PFS; B, NLR < cutoff value versus NLR≥ cutoff value for OS.…”
Section: Combined Resultsmentioning
confidence: 98%
“…As there were several studies 16,18,19,28,33,35 set the cutoff value of pre-treatment NLR being 5, we used the value of 5 to find out the influence of different cutoff value on PFS and OS. The studies 16-19,26,28,32,33,35,36 included reported the HRs of high NLR versus low NLR on PFS in the treatment of advanced NSCLC.…”
Section: Combined Resultsmentioning
confidence: 99%
“…38 Meanwhile, Nivolumab and Pembrolizumab are the recently approved immune checkpoint blockades for treating advanced non-small cell lung cancer after failure of traditional chemotherapy or not. 3 Several clinical studies 17,18,20,39 assessed relationship between NLR and immunotherapy, and some of them 17,18,20 argued that NLR could serve as a predictive factor while other found negative results. 39 Could NLR be a candidate for predicating prognosis of Nivolumab in NSCLC?…”
Objective: Nivolumab has been used for treating non-small cell lung cancer (NSCLC) worldwide. Whether neutrophil-lymphocyte ratio (NLR) can predict the prognosis of NSCLC treated with Nivolumab is still under debate. This meta-analysis was to assess the significance of NLR as a predictive factor in NSCLC patients receiving Nivolumab.Methods: Databases including PubMed, Embase, and the Cochrane library were searched to identify eligible studies evaluating the role of NLR in predicting prognosis of NSCLC treated with Nivolumab until March 2018 without language restrictions. The meta-analysis was performed using hazard ratio (HR) of progression free survival (PFS) and overall survival (OS) in NSCLC patients with various NLR.Results: A total of 14 retrospective studies consisting of 1225 NSCLC patients were included. The combined results showed that relatively higher baseline NLR was associated with poor PFS (HR = 1.44; 95% confidence interval (CI):1.18–1.77; p < 0.05) and OS (HR = 1.75; 95% CI: 1.33–2.30; p < 0.05) after treatment of Nivolumab. Subgroup analysis suggested that NLR ≥ 5 was more reliable for PFS (HR = 1.73; 95%CI: 1.14, 2.62; p < 0.05) and OS (HR = 1.76; 95%CI: 1.47, 2.10; p < 0.05). In addition, post-treatment NLR also had predictive roles for PFS (HR = 3.17; 95%CI: 1.48, 6.82; p < 0.05) and OS (HR = 2.26; 95%CI: 1.05, 4.86; p < 0.05).Conclusion: Our findings suggest that NLR can be used as a prognostic biomarker for NSCLC treating with Nivolumab, and the recommended cutoff value of NLR is 5.
“…As shown in Figure 2B, the pooled HRs of OS from eight studies 16,18,19,28,30,33,35,36 using random effect model was 1.75(95%CI: 1.33, 2.30), favoring NSCLC patients with low pre-treatment NLR.10.1080/2162402X.2018.1507262-F0002Figure 2.Comparisons of PFS and OS in Nivolumab treated NSCLC patients with different baseline NLR. A, NLR < cutoff value(low NLR) versus NLR≥ cutoff value(high NLR) for PFS; B, NLR < cutoff value versus NLR≥ cutoff value for OS.…”
Section: Combined Resultsmentioning
confidence: 98%
“…As there were several studies 16,18,19,28,33,35 set the cutoff value of pre-treatment NLR being 5, we used the value of 5 to find out the influence of different cutoff value on PFS and OS. The studies 16-19,26,28,32,33,35,36 included reported the HRs of high NLR versus low NLR on PFS in the treatment of advanced NSCLC.…”
Section: Combined Resultsmentioning
confidence: 99%
“…38 Meanwhile, Nivolumab and Pembrolizumab are the recently approved immune checkpoint blockades for treating advanced non-small cell lung cancer after failure of traditional chemotherapy or not. 3 Several clinical studies 17,18,20,39 assessed relationship between NLR and immunotherapy, and some of them 17,18,20 argued that NLR could serve as a predictive factor while other found negative results. 39 Could NLR be a candidate for predicating prognosis of Nivolumab in NSCLC?…”
Objective: Nivolumab has been used for treating non-small cell lung cancer (NSCLC) worldwide. Whether neutrophil-lymphocyte ratio (NLR) can predict the prognosis of NSCLC treated with Nivolumab is still under debate. This meta-analysis was to assess the significance of NLR as a predictive factor in NSCLC patients receiving Nivolumab.Methods: Databases including PubMed, Embase, and the Cochrane library were searched to identify eligible studies evaluating the role of NLR in predicting prognosis of NSCLC treated with Nivolumab until March 2018 without language restrictions. The meta-analysis was performed using hazard ratio (HR) of progression free survival (PFS) and overall survival (OS) in NSCLC patients with various NLR.Results: A total of 14 retrospective studies consisting of 1225 NSCLC patients were included. The combined results showed that relatively higher baseline NLR was associated with poor PFS (HR = 1.44; 95% confidence interval (CI):1.18–1.77; p < 0.05) and OS (HR = 1.75; 95% CI: 1.33–2.30; p < 0.05) after treatment of Nivolumab. Subgroup analysis suggested that NLR ≥ 5 was more reliable for PFS (HR = 1.73; 95%CI: 1.14, 2.62; p < 0.05) and OS (HR = 1.76; 95%CI: 1.47, 2.10; p < 0.05). In addition, post-treatment NLR also had predictive roles for PFS (HR = 3.17; 95%CI: 1.48, 6.82; p < 0.05) and OS (HR = 2.26; 95%CI: 1.05, 4.86; p < 0.05).Conclusion: Our findings suggest that NLR can be used as a prognostic biomarker for NSCLC treating with Nivolumab, and the recommended cutoff value of NLR is 5.
“…Many studies have shown that low baseline NLR and ANC predict the efficacy of nivolumab therapy in various cancers . More recent studies have shown that an early decrease in NLR during treatment with PD‐1 inhibitors predicts its efficacy . NLR and ANC have been reported to correlate with the number of circulating MDSCs and tumor‐associated neutrophils, which suppress the function of antitumor T cells .…”
Section: Discussionmentioning
confidence: 99%
“…However, we did not clarify the mechanisms that created these synergistic effects during nivolumab treatment. Several studies have shown that the neutrophil‐to‐lymphocyte ratio (NLR) and the absolute neutrophil count (ANC) in the blood can predict the efficacy of PD‐1 inhibitors in patients with NSCLC . NLR and ANC have also been reported to reflect the number of circulating myeloid‐derived suppressor cells (MDSCs) and tumor‐associated neutrophils, which inhibit the function of antitumor T cells .…”
Several recent studies have shown that salvage chemotherapy following PD‐1 blockade produces high antitumor activity in some patients with non‐small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil‐to‐lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid‐derived suppressor cells and tumor‐associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time‐series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non‐responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non‐responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD‐1 blockade and chemotherapy.
IMPORTANCE Previous studies have suggested the importance of the baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level as prognostic markers. The lung immune prognostic index (LIPI) was shown to be associated with progression-free survival (PFS) and overall survival (OS) among patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) but not cytotoxic chemotherapy (CCT). OBJECTIVE To determine whether the LIPI is associated with long-term outcomes in pooled analyses of clinical studies of ICI and targeted therapy (TT) for patients with mNSCLC. DESIGN, SETTING, AND PARTICIPANTS An exploratory pooled analysis was performed of the LIPI on data from 11 randomized clinical multinational trials evaluating ICIs and TT submitted to the US Food and Drug Administration between January 1, 2013, and December 31, 2017, for 4914 patients with mNSCLC. Lung immune prognostic index scores were calculated based on the dNLR and the LDH level per previous publications to generate good, intermediate, and poor composite scores. Multivariable Cox proportional PFS and OS hazard ratios were generated for the dNLR, the LDH level, age, smoking status, histologic characteristics, and Eastern Cooperative Oncology Group performance score. MAIN OUTCOMES AND MEASURES Overall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores. RESULTS Eleven mNSCLC randomized trials were analyzed, including 3987 patients with available data. In 5 ICI trials comprising 2440 patients, 1368 patients received ICIs and 1072 patients received CCT. In 6 TT trials comprising 1547 patients, 1110 patients received TT and 437 patients received CCT. A good LIPI score was associated with better OS among patients receiving ICIs (hazard ratio, 0.34; 95% CI, 0.28-0.42), TT (hazard ratio, 0.28; 95% CI, 0.21-0.37), and CCT (hazard ratio, 0.49; 95% CI, 0.40-0.60 in ICI trials; hazard ratio, 0.41; 95% CI, 0.27-0.61 in TT trials) than those with poor LIPI scores. Similar findings were observed in terms of PFS (ICIs: hazard ratio, 0.59; 95% CI, 0.48-0.72; TT: hazard ratio, 0.46; 95% CI, 0.37-0.57; and CCT: hazard ratio, 0.56; 95% CI, 0.45-0.68 in ICI trials; hazard ratio, 0.51; 95% CI, 0.38-0.69 in TT trials). CONCLUSIONS AND RELEVANCE The baseline LDH level and dNLR are important prognostic biomarkers irrespective of treatment modality for patients with mNSCLC. As further prospective clinical trial information is collected, the role of the LIPI score can be better defined.
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