Pathological evaluation of tumor infiltrating lymphocytes and the benefit of nivolumab in advanced non-small cell lung cancer (NSCLC)

Abstract

Background: Assessment of tumor infiltrating lymphocytes (TIL) by pathologists using Hematoxylin-Eosin (H&E), has been described as a prognostic factor in resected NSCLC. We aimed to correlate TIL to the benefit from nivolumab in patients (pts) with treated advanced NSCLC. Methods: Patients with advanced NSCLC treated with nivolumab, with biopsy available for evaluation, were included between November 2012 and February 2017 in two cancer centers. Patients characteristics and outcome were collected. The percentage of tumor infiltrating lymphocytes in the stroma was evaluated using H&E staining from archival pretreatment tumor tissue samples. Primary endpoint was to correlate TIL density with progression free survival (PFS). Results: Out of ninety-eight patients included. 60 (61%) pts were male, with median age of 61 years and 85 (89%) were smokers. Sixty three (73%) pts were PS 0-1. Sixty tumors (61%) were adenocarcinoma, 29 (30%) squamous and 9 (10%) other histologies. Among 83 tumors with known molecular profile, 22 (27%) were KRAS mutated 7 (8%) EGFR mutated, 1(1%) ALK positive. The median treatment line was 3 (2-4). The median follow up was 8 months (m)(95%CI[6-19]). The median PFS was 2m (95%CI[1-5]). The ORR was for 16%. The median TIL density was 5% (2-15). TIL density ≥5% correlated with PFS in univariate and multivariate analysis (HR: 0.48 [0.28-0.82] p=0.007 and HR:0.31 [0.14-0.68] p=0.004 respectively). TIL density ≥5% was also associated with better ORR (OR=3.5, 95%CI [1.06-11.7], p=0.04). Conclusions: Pathological assessment of TIL allows an easy evaluation of immune infiltration in NSCLC and independently correlates PFS in NSCLC pts treated with nivolumab. Results from validation cohorts and combination with other morphological and immunohistochemical parameters will be reported.