Predictive factors for progression-free survival in non-small cell lung cancer patients receiving nivolumab based on performance status.

Nivolumab has promising efficacy for the treatment of non-small cell lung cancer (NSCLC). Various predictive factors for nivolumab response in those with NSCLC have been reported, including performance status (PS). The objective of this retrospective study was to determine the predictive factors for nivolumab response in those with NSCLC with good PS and those with poor PS. We retrospectively collected pretreatment clinical data of 296 consecutive patients with NSCLC treated with nivolumab. We investigated the relationship between progression-free survival (PFS) and patient characteristics and analyzed predictive factors associated with good PS (PS 0-1) or poor PS (PS 2-4). The median age of patients was 70 years; 206 patients were male, and 224 were classified as having good PS (PS 0-1). The median PFS was 3.0 months, 3.7 months, and 1.2 months for all patients, patients with good PS, and patients with poor PS respectively. Multivariate analysis showed that never smoking (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.15-2.75), high C-reactive protein (CRP) (HR, 1.39; 95% CI, 1.00-1.93), liver metastasis (HR, 1.95; 95% CI, 1.24-3.07), pleural effusion (HR, 1.45; 95% CI, 1.06-2.00), and steroid use (HR, 2.85; 95% CI, 1.65-4.94) were associated with significantly shorter PFS in patients with good PS. A high advanced lung cancer inflammation index (ALI) was significantly associated with longer PFS in patients with poor PS (HR, 0.24; 95% CI, 0.08-0.79). In patients with NSCLC treated with nivolumab, the factors found to be predictive of shorter PFS in patients with good PS were never smoking, high CRP, liver metastasis, pleural effusion, and steroid administration, whereas high ALI was predictive of longer PFS in patients with poor PS.

Adachi Y ，Tamiya A ，Taniguchi Y ，Enomoto T ，Azuma K ，Kouno S ，Inagaki Y ，Saijo N ，Okishio K ，Atagi S ... -  《Cancer Medicine》

Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44-5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice.

Shiroyama T ，Suzuki H ，Tamiya M ，Tamiya A ，Tanaka A ，Okamoto N ，Nakahama K ，Taniguchi Y ，Isa SI ，Inoue T ，Imamura F ，Atagi S ，Hirashima T ... -  《Cancer Medicine》

The efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer with liver metastases.

Kitadai R ，Okuma Y ，Hakozaki T ，Hosomi Y ... -  《-》

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 ... -  《-》

Prognostic value of morphological characteristics assessed by CT scan in patients with non-small cell lung cancer treated with nivolumab.

Nivolumab is known to demonstrate superior overall survival compared with docetaxel in pretreated non-small cell lung cancer (NSCLC) patients. Programmed death-ligand 1 (PD-L1) expression is reported to predict the outcome of treatment by nivolumab in lung cancer patients. However, the significance of the morphological characteristics of chest computed tomography (CT) as predictors of nivolumab efficacy for advanced NSCLC patients remains unknown. We performed a multicenter retrospective trial from April 2013 to March 2017, to assess the significance of CT morphological characteristics as predictors of nivolumab efficacy for advanced NSCLC patients. A total of 78 NSCLC patients pretreated with nivolumab were enrolled. A chest radiologist used chest CT to assess the following morphological characteristics of each patient's main tumor and intrathoracic status prior to nivolumab treatment; interstitial septal thickening, peritumoral ground-glass opacity, spiculated margin, air bronchogram, cavity or necrosis, adjacent organ invasion, bulky lymph node, and accumulation of small lymph nodes. Logistic regression and Cox proportional hazards regression models were used to analyze outcomes. A total of 60 (77%) patients were male and 72 (92%) had a performance status (PS) of 0 or 1. The objective response rates of male patients and heavy smokers were significantly higher than those of female patients and light or never smokers, respectively. Multivariate analysis identified light or never smoking, poor PS, histological type of squamous cell carcinoma, and interstitial septal thickening as independent negative predictors of progression free survival (PFS). Interstitial septal thickening was a significant and independent predictor of PFS in NSCLC patients treated with nivolumab. SIGNIFICANT FINDINGS OF THE STUDY: Interstitial septal thickening is an independent predictor of progression free survival in non-small lung cancer patients treated with nivolumab. The current study reveals the significance of morphological characteristics obtained via chest computed tomography as a predictor of nivolumab efficacy for advanced non-small cell lung cancer patients.

Minemura H ，Moriya H ，Imai H ，Sugiyama T ，Yamada Y ，Higuchi M ，Kaira K ，Ozaki Y ，Kanazawa K ，Yokouchi H ，Kasai T ，Kaburagi T ，Suzuki H ，Minato K ，Shibata Y ... -  《-》