P3.02c-053 Clinical and Plasma Biomarkers for Disease Control with Nivolumab Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC): Topic: IT

Abstract

Anti-PD1 antibodies have become the treatment of choice for most advanced NSCLC patients after failure of first line platinum-based chemotherapy. Responses are seen in roughly 20% of treated patients. PDL1 expression level and mutational burden might be predictive factors but are not always available and their predictive accuracy is limited. Predictive biomarkers are urgently needed. We hypothesized that clinical data and baseline blood tests might be predictive for benefit from nivolumab. A chart review was performed of patients with advanced NSCLC who received at least one cycle of nivolumab, at one of three cancer centers during 2015-2016. Additional inclusion criteria were: available baseline clinical data, evaluation of response and availability of blood test results. Blood test results collected were: Absolute Lymphocyte Count (ALC), Absolute Neutrophil Count (ANC), White Blood Cells (WBC), Hemoglobin (Hb), Platelets (PLT), Albumin (ALB), Lactate Dehydrogenase (LDH). Blood test results were collected at baseline and before the second and third treatment. Disease control (DC) was defined as any tumor shrinkage, or stable disease for at least 6 months, as assessed by the treating physician by computerized tomography scans. Patients with DC were compared with patients with progressive disease (PD, patients progressing within the first 6 months). Uni- and multivariate regression analyses were performed using Stata (version 11.2, StataCorp). A total of 70 patients treated with nivolumab were included, median age 67 years, 66% males, 27% with DC. DC patients compared to PD patients were younger (61.6 vs 69.3 yr, p<0.001), more females (42% vs 27%, p<0.05), and had a lower baseline WBC (6.9 vs 9.2 K/microL, p<0.05). The difference in WBC between DC and PD patients increased during treatment (2.3 K/microL at baseline, 2.6 prior to third treatment). Lower baseline neutrophil count was associated with DC (p=0.02). Neither performance status nor LDH predicted outcome on uni-variate analysis. On multivariate analysis age (p=0.050) and baseline WBC (p=0.02) were associated with outcome. Patients less than 67 years of age with baseline WBC<8.04 K/microL (n=18) had DC rate of 50%, while DC rate was 4% in patients 67 years or more, with WBC >=8.04 K/microL (n=23). We have identified clinical biomarkers (age and baseline WBC) that are associated with DC under nivolumab treatment. Validation on an independent data set is warranted. The association of a low peripheral WBC/ANC with increased response rate raises the possibility that acute inflammatory responses are counteractive to anti-PD1 therapy.