Nivolumab in Non-Small Cell Lung Cancer: Real World Long-Term Survival Results and Blood-Based Efficacy Biomarkers

Abstract

ObjectivesWe aimed to examine clinical data and baseline blood test results as potential predictive biomarkers for benefit from nivolumab, in advanced non-small cell lung cancer patients (NSCLC).Materials and MethodsA chart review was performed of 108 advanced NSCLC patients who commenced treatment with nivolumab between 2015-6 at three Israeli cancer centers, and for whom laboratory tests results were available. Data collected included sex, age, ECOG-PS, histology and number of previous lines of treatment. Baseline blood test results collected: absolute lymphocyte and neutrophil count (ANC), white blood cells (WBC), hemoglobin, platelets, albumin and lactate dehydrogenase (LDH). Neutrophil to Lymphocyte Ratio and ‘derived NLR’ (dNLR = (ANC/[WBC-ANC])) were calculated. Disease control at six months (DC6) was defined as any tumor shrinkage or stable disease during the first six months of nivolumab treatment. The association between clinical/laboratory variables and survival was tested with a Cox proportional hazard model. Data cut-off occurred in November 2019.Results35 patients (32.4%) achieved DC6. Median overall survival (OS) of entire study population was 5.4 months. Four year survival rate was 16%. Achievement of DC6 strongly correlated with longer OS (HR 0.12, 95% C.I. 0.07-0.21, p<0.001). In univariate and multivariate analysis, dNLR, albumin and LDH correlated significantly with OS. No variables correlated significantly with DC6 in multivariate analysis. Based on albumin and LDH, we produced a score called CLAS (combined LDH and albumin score), including four prognostic groups of patients. Patients having low albumin and high LDH had the worst prognosis.ConclusionIn real-life setting, long-term efficacy of nivolumab in advanced line treatment of NSCLC is consistent with clinical trials. Response or stability of disease during first six months of treatment is associated with prolonged survival. We propose a novel score (CLAS) that may be useful for predicting outcome in nivolumab-treated NSCLC patients, but further validation is required.

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy

“…The prognostic role of LDH is well-defined in melanoma patients treated with ICIs, and the LDH levels are being used as stratification criteria in melanoma clinical trials [ 31 , 48 , 49 , 50 ]. Similarly, a worse prognosis was observed in ICI-treated patients with other indications, such as NSCLC and RCC in the observational studies [ 31 , 51 , 52 , 53 , 54 ]. The LDH levels were included in some of the prognostic models, albeit with different cutoffs (>ULN vs. >2× ULN) used for patient dichotomization [ 55 ].…”

Predictors of early mortality risk in patients with epithelial ovarian cancer

“… 26 However, the current study failed to demonstrate the role of parity as an independent risk predictor of mortality in patients with EOC. Many recent studies have also shown that certain hematologic markers, can be used to identify individuals with a high risk of death from some tumors 27 , 28 , 29 including EOC. 11 , 30 The measurement of preoperative hematological markers is cheap, noninvasive, and relatively easy compared to using genetic molecular biomarkers.…”

Circulating Biomarkers for Therapeutic Monitoring of Anti-cancer Agents

“… 26-28 Conversely, a low blood NLR is associated with longer survival in patients with metastatic melanoma with brain involvement or advanced non–small-cell lung cancer (NSCLC) treated with PD-1-targeted therapies. 29 , 30 NLR has also been investigated in aggregate with other markers. Ren et al showed among advanced NSCLC patients with TMB > 10 mutations/Mb, those with NLR ≤ 2.5 had significantly more favorable overall survival (OS) and progression-free survival (PFS) compared with patients with NLR > 2.5.…”