Abstract LB-072: Impact of baseline serum cytokines on survival in patients (pts) with advanced squamous (SQ) non-small cell lung cancer (NSCLC) treated with nivolumab (nivo) or docetaxel (doc): Exploratory analyses from CheckMate 063 and CheckMate 017
Authors: Farsaci Benedetto , Geese William J. , Desai Kaushal D. , Jin Chelsea , Antonia Scott J. , Lena Hervé , Horn Leora , Planchard David , Reckamp Karen L. , Stinchcombe Thomas E. , Gettinger Scott , Borghaei Hossein , Hellmann Matthew D. , Harbison Christopher , Xu Dong , Blackwood-Chirchir M. Anne , Rizvi Naiyer 
Published: July 2016

Abstract
Background: Nivo, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, is approved in the United States and European Union for the treatment of pts with advanced SQ NSCLC refractory to prior chemotherapy, based on results of phase 2 (CheckMate 063) and phase 3 (CheckMate 017) trials. In these studies, PD-1 ligand (PD-L1) expression was neither predictive nor prognostic of survival benefit. Here we present results of exploratory analyses from these studies evaluating the potential correlation of baseline serum cytokines with overall survival (OS) in pts with SQ NSCLC.
Methods: Baseline serum cytokine concentrations in evaluable pts from CheckMate 063 and CheckMate 017 treated with nivo (n = 222) or doc (n = 118) were analyzed using a custom HumanMAP quantitative multiplexed immunoassay (Myriad RBM, Austin, TX). Multivariate analyses using a stepwise variable selection were performed in a Cox model using a 6:4 training:test validation in nivo-treated subjects. The performance of the association with OS of the identified cytokine set in nivo-treated subjects was tested using time-varying receiver-operating characteristic (ROC) analysis. SQ-cytoscore, generated to quantify the effect of the identified cytokine set on OS, was computed as follows: 1) calculation of the tertile bin distribution of each cytokine in the set in all pts and assignment of a point score (0, 1, or 2) for each tertile expression of each cytokine; 2) calculation of SQ-cytoscore for each pt as the sum of points; 3) categorization of pts as SQ-cytoscore “high” or “low” based on the median cutoff. OS was analyzed in pts with high vs low SQ-cytoscore treated with nivo and doc using the Kaplan-Meier method and 18-mo data cutoffs for CheckMate 063 (June 2015) and CheckMate 017 (August 2015).
Results: Of 26 evaluable baseline cytokines, a set of 14 was identified to be associated with OS. Median OS was longer in pts with high vs low SQ-cytoscore in both nivo- and doc-treated cohorts (nivo [n = 102 vs 120]: 15.6 vs 5.3 months, HR:0.48, 95%CI:0.36-0.64, P&lt;0.0001; doc [n = 70 vs 48]: 9.1 vs 4.9 months (HR:0.39, 95%CI:0.27-0.56, P&lt;0.0001). Among pts with high SQ-cytoscores (n = 172), median OS was 15.6 vs 9.1 months (HR:0.63, 95%CI:0.45-0.88, P = 0.0051) for nivo- vs doc-treated pts, respectively. Among pts with low SQ-cytoscores (n = 168), median OS was 5.3 vs 4.9 months (HR:0.51, 95%CI:0.37-0.71, P = 0.0009) for nivo- vs doc-treated pts, respectively.
Conclusion: In pts with advanced SQ NSCLC pooled from 2 clinical trials, a set of serum cytokines (details to be presented) potentially associated with OS benefit was identified. The benefit of a high SQ-cytoscore appeared more profound in pts treated with nivo vs doc. These preliminary findings require prospective validation in future studies.
Citation Format: Benedetto Farsaci, William J. Geese, Kaushal D. Desai, Chelsea Jin, Scott J. Antonia, Hervé Lena, Leora Horn, David Planchard, Karen L. Reckamp, Thomas E. Stinchcombe, Scott Gettinger, Hossein Borghaei, Matthew D. Hellmann, Christopher Harbison, Dong Xu, M. Anne Blackwood-Chirchir, Naiyer Rizvi. Impact of baseline serum cytokines on survival in patients (pts) with advanced squamous (SQ) non-small cell lung cancer (NSCLC) treated with nivolumab (nivo) or docetaxel (doc): Exploratory analyses from CheckMate 063 and CheckMate 017. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-072.