Smoking History as a Potential Predictor of Immune Checkpoint Inhibitor Efficacy in Metastatic Non-Small Cell Lung Cancer

被引：49

作者：

Wang, Xinan ^{[1
,2
]}

Ricciuti, Biagio ^{[3
,4
]}

Alessi, Joao, V ^{[3
,4
]}

Nguyen, Tom ^{[3
,4
]}

Awad, Mark M. ^{[3
,4
]}

Lin, Xihong ^{[5
]}

Johnson, Bruce E. ^{[3
,4
]}

Christiani, David C. ^{[2
,6
]}

机构：

[1] Harvard Univ, Grad Sch Arts & Sci, Cambridge, MA 02138 USA

[2] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA

[3] Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA

[4] Harvard Med Sch, Ctr Canc Genom, Dana Farber Canc Inst, Boston, MA 02115 USA

[5] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[6] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2021年 / 113卷 / 12期

基金：

美国国家卫生研究院;

关键词：

TUMOR MUTATIONAL BURDEN; SURVIVAL; BLOCKADE; IMMUNOTHERAPY; REGRESSION; NIVOLUMAB;

D O I：

10.1093/jnci/djab116

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 programmed death ligand-1 (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 to 1.36, P<.001; progression-free survival hazard ratio = 0.92, 95% CI = 0.88 to 0.95, P<.001; overall survival hazard ratio = 0.94, 95% CI = 0.90 to 0.99, P=.01). Predictive models incorporating pack-years and PD-L1 TPS yielded additional information and achieved similar model performance compared with 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.

引用

页码：1761 / 1769

页数：9

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