Xinan Wang1,2, Biagio Ricciuti3, Joao V Alessi3, Tom Nguyen3, Mark M Awad3, Xihong Lin4, Bruce E Johnson3, David C Christiani2,5. 1. The Graduate School of Arts and Sciences, Harvard University, 1350 Massachusetts Ave, Cambridge, MA, USA. 2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, USA. 3. Lowe Center for Thoracic Oncology and Center for Cancer Genomics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, USA. 4. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave, Boston, MA, USA. 5. Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Despite the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients, consistent and easily obtainable predictors of efficacy remain elusive. METHODS: This study was conducted on 644 advanced non-small cell lung cancer (NSCLC) patients treated with ICI monotherapy between April 2013 and September 2020 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital. Patient smoking history, clinicopathological characteristics, tumor mutation burden (TMB) by clinical targeted next generation sequencing, and PD-L1 tumor proportion score (TPS) by immunohistochemistry were prospectively collected. The association of smoking history with clinical outcomes of ICI monotherapy in metastatic NSCLC patients was evaluated after adjusting for other potential predictors. All statistical tests were 2-sided. RESULTS: Of 644 advanced NSCLC patients 105 (16.3%) were never smokers, 375 (58.2%) were former smokers (median pack-years = 28), and 164 (25.4%) were current smokers (median pack-years = 40). Multivariable logistic and Cox proportional hazards regression analyses suggested that doubling of smoking pack-years is statistically significantly associated with improved clinical outcomes of patients treated with ICI monotherapy (objective response rate odds ratio = 1.21, 95% confidence interval [CI] = 1.09-1.36, P < .001; progression-free survival hazard ratio = 0.92, 95% CI = 0.88-0.95, P < .001; overall survival hazard ratio = 0.94, 95% CI = 0.90-0.99, P = .01). Predictive models incorporating pack-years and PD-L1 TPS yielded additional information and achieved similar model performance compared to using TMB and PD-L1 TPS. CONCLUSIONS: Increased smoking exposure had a statistically significant association with improved clinical outcomes in metastatic NSCLC treated with ICI monotherapy independent of PD-L1 TPS. Pack-years may serve as a consistent and readily obtainable surrogate of ICI efficacy when TMB is not available to inform prompt clinical decisions and allow more patients to benefit from ICIs.
BACKGROUND: Despite the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients, consistent and easily obtainable predictors of efficacy remain elusive. METHODS: This study was conducted on 644 advanced non-small cell lung cancer (NSCLC) patients treated with ICI monotherapy between April 2013 and September 2020 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital. Patient smoking history, clinicopathological characteristics, tumor mutation burden (TMB) by clinical targeted next generation sequencing, and PD-L1 tumor proportion score (TPS) by immunohistochemistry were prospectively collected. The association of smoking history with clinical outcomes of ICI monotherapy in metastatic NSCLC patients was evaluated after adjusting for other potential predictors. All statistical tests were 2-sided. RESULTS: Of 644 advanced NSCLC patients 105 (16.3%) were never smokers, 375 (58.2%) were former smokers (median pack-years = 28), and 164 (25.4%) were current smokers (median pack-years = 40). Multivariable logistic and Cox proportional hazards regression analyses suggested that doubling of smoking pack-years is statistically significantly associated with improved clinical outcomes of patients treated with ICI monotherapy (objective response rate odds ratio = 1.21, 95% confidence interval [CI] = 1.09-1.36, P < .001; progression-free survival hazard ratio = 0.92, 95% CI = 0.88-0.95, P < .001; overall survival hazard ratio = 0.94, 95% CI = 0.90-0.99, P = .01). Predictive models incorporating pack-years and PD-L1 TPS yielded additional information and achieved similar model performance compared to using TMB and PD-L1 TPS. CONCLUSIONS: Increased smoking exposure had a statistically significant association with improved clinical outcomes in metastatic NSCLC treated with ICI monotherapy independent of PD-L1 TPS. Pack-years may serve as a consistent and readily obtainable surrogate of ICI efficacy when TMB is not available to inform prompt clinical decisions and allow more patients to benefit from ICIs.
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