Abstract 1691: Clinical characteristics influencing survival in stage-IV non-small cell lung cancer treated with nivolumab: A single-institutional experience
Authors: Naqash Abdul Rafeh , Stroud Chipman R. , Yang Li V. , Muzaffar Mahvish , Walker Paul R. 
Published: August 2018

Abstract
Background: Immune-checkpoint blockade (ICB) using antibodies directed against the programmed cell death-1 (PD-1) axis has revolutionized the management of non-small cell lung cancer (NSCLC). Based on results from the Checkmate 017 and 057, nivolumab, an anti-PD-1 antibody, has emerged as the standard of care in the second line setting for advanced NSCLC. However, the lack of uniform responses as noted in daily practice suggests clinical heterogeneity. Hence, it is essential to identify characteristics that may predict inferior efficacy to ICB. Methods: Retrospectively we identified 61 stage IV NSCLC patients treated with nivolumab from April 2015 to March 2017 after progressing on a platinum doublet. These patients were part of an ongoing institutionally approved prospective biomarker-based study. Follow up cutoff for survival analysis was set on October 1, 2017. Overall survival after immunotherapy (OSI) was defined as the time from ICB initiation to last follow up or death. Cox regression was used to assess the correlation of clinical and biochemical factors influencing OSI. Results: The median age was 63 years with predominant histology being adenocarcinoma in 65.6 %. A majority of patients were of Caucasian ethnicity (68.9%) and male gender (60.7%). Skeletal involvement (54.1 %), liver (27.9 %) and brain (26.2 %) were the most common metastatic compartments. Simultaneous involvement of greater than 1 metastatic compartment at ICB initiation was observed in 54.1% of patients. Approximately 67.3 % patients were either former/never smoker at the time of nivolumab initiation. The median OSI for our NSCLC cohort treated with nivolumab was 6.3 months. On adjusted Cox univariate analysis of the clinically relevant covariates, baseline factors present at anti-PD-1 initiation that were associated with inferior OSI were age greater than 65 [p= 0.036; 2.37 (1.05-5.30)], brain metastasis [p=0.014; 3.30 (1.25-7.37)] and greater than 1 metastatic compartment involvement [P=0.041; 2.78 (1.04-7.44). Using adjusted multivariate Cox regression model with backward elimination, all three factors were noted to be independently associated with inferior OSI.Conclusions: Our study identified subgroups with certain baseline clinical features that tend to behave poorly despite ICB. This suggests that improving outcomes in such subgroups may require exploring strategies involving combination ICB or other novel targeted therapies. Also, better identification of such subgroups via larger datasets may help in the appropriate designation of patients for optimally tailored ICB and thus assist in improving outcomes in NSCLC.
Citation Format: Abdul Rafeh Naqash, Chipman R. Stroud, Li V. Yang, Mahvish Muzaffar, Paul R. Walker. Clinical characteristics influencing survival in stage-IV non-small cell lung cancer treated with nivolumab: A single-institutional experience [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1691.