Abstract 370: Smoking history as an independent predictor for immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC)

Abstract

Abstract Importance: Immune Checkpoint Inhibitors (ICIs) induce durable response in a subset of non-small cell lung cancer (NSCLC) patients. There is an unmet need to develop effective predictors for ICIs in metastatic NSCLC. Objective: Define the predictive impact of smoking history (pack-years) on the clinical outcomes of ICI monotherapy and further to validate the potential clinical utility in metastatic NSCLC. Design, setting, and participants: This study was conducted on 680 metastatic NSCLC patients treated with ICIs between April 2013 and September 2020 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital. Patient TMB and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) were determined by clinical targeted Next Generation Sequencing (NGS) and immunohistochemistry (IHC) and detailed smoking history and clinicopathological characteristics were prospectively collected. Main outcomes and measures: Evaluation of the association of smoking pack-years with objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients treated with ICI monotherapy. Assessment of time-dependent area under the curve (AUC) for predictive models of clinical outcomes. Results: Among 680 metastatic NSCLC patients who received ICI monotherapy: 109 (16.0%) never smokers, 397 (58.4%) former smokers [median 30 pack-years], and 174 (25.6%) current smokers [median 40 pack-years]. Multivariable analysis suggested that doubling of smoking pack-years is significantly associated with better clinical outcomes of ICIs. (ORR OR = 1.20, P < 0.001; PFS HR = 0.92, P < 0.001; OS HR = 0.94, P = 0.01) Predictive models incorporating smoking pack-years yielded additional information and achieved similar model performance compared to the one using TMB. Conclusions and Relevance: This finding suggests that detailed smoking information has a significant predictive value on clinical outcomes of ICI monotherapy independent of PD-L1 TPS. Smoking pack-years could serve as a non-invasive and consistent surrogate for TMB when it is not readily available for treatment-decision in metastatic NSCLC. Citation Format: Xinan Wang, Biagio Ricciuti, Joao V. Alessi, Tom Nguyen, Mark M. Awad, Xihong Lin, Bruce E. Johnson, David C. Christiani. Smoking history as an independent predictor for immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 370.