Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Immunotherapeutic efficacy in NSCLC and patients’ smoking status: A meta-analysis.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20510)
Author(s): Shanshan Wang, Guoqiang Wang, Yu Xu, Shangli Cai, Jianping Xiong; Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, China; The Medical Department, 3D Medicines Inc., Shanghai, China; The Medical Department, 3D Medicines Inc., Beijing, China; Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China
Background: In non-small cell lung cancer (NSCLC), tumour mutational burden (TMB) has been validated in predicting the clinical benefit of immunotherapy. Smoke, delivering the carcinogens that form covalently bound DNA adducts into respiratory system, is the critical cause of miscoding events and mutational burden in NSCLC. However, the predictive potential of tobacco consumption in immunotherapy remains controversial. Here, we did a meta-analysis to assess the heterogeneity of immune checkpoint inhibitor (ICI) efficacy in NSCLC patients with or without smoking habit. Methods: We systematically searched PubMed, the Cochrane Central library and Embase, for the randomized controlled trials (RCTs) of ICIs (inhibitors of PD-1, PD-L1, CTLA-4, or combination) in NSCLC. The studies were excluded due to the unpublished hazard ratio (HR) for both progression-free survival (PFS) and overall survival (OS) according to smoking status. Pooled estimates of survival HR and 95% confidence interval (CI) in smokers and non-smokers were performed using a random-effects model, and the heterogeneity between the two estimates was assessed using an interaction test by Review Manager. Results: In total, 13 eligible RCTs of FDA-approved ICIs (concerning ipilimumab, nivolumab, pembrolizumab, atezolizumab, and avelumab) containing 8154 patients with NSCLC (6800 [83.4%] smokers and 1354 [16.6%] non-smokers) were included for analysis. Compared to standard treatment, a prolonged PFS was observed in smokers treated with ICIs (pooled HR, 0.72, 95% CI 0.63-0.81, P < 0·001) instead of non-smokers (pooled HR, 0.98, 95% CI 0.73-1.31, P = 0·90). The pooled HR of OS between immunotherapy and standard treatment was 0.77 (95% CI 0.69-0.86, P < 0·001) in smokers and 0.78 (95%CI 0.59-1.02, P = 0·07) in non-smokers. Similar results were observed among sub-groups according to the different histology (squamous and non-squamous), class of ICIs (anti-PD-1 or PD-L1) and lines of treatment (first-line or subsequent). The difference in efficacy between smokers and non-smokers treated with ICIs was also significant (HR 0.75, 95% CI 0.62-0.92, P = 0·005). Conclusions: ICIs can improve PFS and OS for patients with advanced NSCLC, but the magnitude of benefit depends on smoking history, especially for PFS. Future clinical trials are supposed to include more non-smokers and concentrate on enhancing the efficacy of ICIs in the NSCLC patients without cigarette consumption, possibly discovering distinctive immunotherapeutic approaches in smokers and non-smokers.