Neutrophil-to-lymphocyte ratio after four weeks of nivolumab administration as a predictive marker in patients with pretreated non-small-cell lung cancer.

Although phase III trials have shown improved overall and progression-free survival (PFS) using nivolumab compared to docetaxel in patients with non-small-cell lung cancer, the progressive disease ratio of nivolumab is higher than docetaxel. Furthermore, nonconventional response patterns of nivolumab make it difficult to determine the time point for nivolumab discontinuation. Therefore, a method to detect non-responders to nivolumab at an early time point is crucial. This retrospective study was conducted to identify immunological and nutritional markers, including neutrophil-to-lymphocyte ratios (NLR), which would predict the efficacy of nivolumab treatment. Because the expression of these markers fluctuates dramatically during treatment, repeat evaluation was performed. We retrospectively investigated 30 patients with non-small-cell lung cancer who were treated with nivolumab. The stratified data of each marker obtained during four weeks after nivolumab treatment were evaluated by Cox proportional hazards regression to verify the differences in PFS. One and four patients experienced progressive disease within two and four weeks, respectively. Therefore, 29 and 26 patients were analyzed two and four weeks after nivolumab administration, respectively. The results showed that the NLR after four weeks could predict PFS. The median PFS in 21 patients with NLR < 5 after four weeks of nivolumab administration was 95 days (95% confidence interval [CI] 50-NA), while the mPFS in five patients with NLR ≥ 5 was 10 days (95% CI 6-NA). NLR ≥ 5 showed a hazard ratio of 5.995 (95% CI 1.225-29.35). Clarifying NLR four weeks after nivolumab administration may be useful to predict outcomes in nivolumab-treated patients.

Takeda T ，Takeuchi M ，Saitoh M ，Takeda S ... -  《-》

Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab.

Immunotherapy with the programmed death receptor-1 (PD-1) antibody nivolumab has changed the field of metastatic non-small cell lung cancer (NSCLC) treatment. Nivolumab shows better outcome compared to standard second line chemotherapy, but reliable prognostic markers are lacking. High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammation and associated with worse overall survival (OS) in several tumor types, but have not been analysed extensively in lung cancer in the era of immunotherapy. Patients with metastatic NSCLC treated with nivolumab were enrolled. Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. Cox regression analyses were conducted to study the prognostic role of NLR and PLR on OS and progression free survival (PFS). Logistic regression was used to study the association of NLR and PLR. The combined impact of NLR and other known prognostic factors was explored with multivariable regression. Fifty-two patients were included. Elevated NLR was associated with worse OS (HR for log(NLR)=3.64, 95% CI 1.78-7.46, p<0.001) and lower response rates (OR for log(NLR)=0.17, 95% CI 0.04-0.68, p=0.013). There was no significant association with PFS (HR for log(NLR)=1.46, 95% CI=0.91-2.34, p=0.114). The AUC for the prediction of 10-month survival using log(NLR) was 0.738, the AUC for the prediction of response to nivolumab was 0.776. Relationships with PLR were similar. NLR and PLR didn't correlate with other known prognostic factors (i.e histology, tobacco use, ECOG performance status,) in our cohort. Inclusion of NLR in multivariable models with these other factors significantly improved the prediction of OS. Elevated pre-treatment NLR and PLR are associated with shorter OS and PFS and with lower response rates in patients with metastatic NSCLC treated with nivolumab independently of other prognostic factors.

Diem S ，Schmid S ，Krapf M ，Flatz L ，Born D ，Jochum W ，Templeton AJ ，Früh M ... -  《-》

Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with advanced non-small-cell lung cancer treated with nivolumab.

Nakaya A ，Kurata T ，Yoshioka H ，Takeyasu Y ，Niki M ，Kibata K ，Satsutani N ，Ogata M ，Miyara T ，Nomura S ... -  《-》

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study.

Russo A ，Russano M ，Franchina T ，Migliorino MR ，Aprile G ，Mansueto G ，Berruti A ，Falcone A ，Aieta M ，Gelibter A ，Russo A ，Barni S ，Maio M ，Martelli O ，Pantano F ，Iacono D ，Calvetti L ，Quadrini S ，Roca E ，Vasile E ，Imperatori M ，Occhipinti M ，Galvano A ，Petrelli F ，Calabrò L ，Pasquini G ，Intagliata S ，Ricciardi GRR ，Tonini G ，Santini D ，Adamo V ... -  《-》

Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab.

Explore markers to predict the clinical outcomes of checkpoint inhibitors have high unmet needs. The following study investigates whether hematologic parameter such as systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) is associated with nivolumab efficacy in advanced non-small-cell lung cancer (NSCLC). Advanced/metastatic NSCLC patients treated with nivolumab monotherapy for second-line or further-line treatment at Jilin Cancer Hospital between March 2016 and July 2018 were enrolled in this retrospective study. The optimal cutoff values of SII, NLR, and PLR for predicting efficacy and prognosis were determined according to receiver operating characteristic (ROC) curve and the areas under the ROC curve. Progression-free survival (PFS) and overall survival (OS) were calculated and compared using Kaplan-Meier method and log-rank test. Prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression (PHR) analyses. A total of 44 patients with advanced NSCLC were included; the median age was 60 (range: 43-74). The optimal cutoff value of SII/NLR/PLR predicted PFS and OS was 603.5, 3.07, and 144. Low SII, NLR, and PLR were associated with longer PFS (HR for SII = 0.34, 95%CI 0.15-0.76, P = 0.006; HR for NLR = 0.46, 95%CI 0.22-0.99, P = 0.048; HR for PLR = 0.39, 95%CI 0.17-0.94, P = 0.025) and OS (HR for SII = 0.16, 95%CI 0.05-0.51, P = 0.005; HR for NLR = 0.20, 95%CI 0.06-0.62, P = 0.002; HR for PLR = 0.20, 95%CI 0.06-0.73, P = 0.008). NLR ≤ 3.07, PLR ≤ 144, SII ≤ 603.5 were independently associated with longer PFS and OS. The SII, NLR, and PLR are promising prognostic predictor for patients with metastatic NSCLC patients.

Liu J ，Li S ，Zhang S ，Liu Y ，Ma L ，Zhu J ，Xin Y ，Wang Y ，Yang C ，Cheng Y ... -  《-》