Abstract
Background The influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. We performed a meta-analysis to evaluate the effect of additional AS in patients with NSCLC taking TKIs. Methods Relevant observational studies were identified by a search of Medline, Embase, and Web of Science databases. Only studies with multivariate analyses were included. A random-effect model was used to combine the results. Results Thirteen retrospective studies with 12259 patients were included. Pooled results showed that concomitant use of AS was associated with worse progression-free survival (PFS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.31 to 1.89, P < 0.001; I2 = 65%) and overall survival (OS, adjusted HR: 1.38, 95% CI: 1.19 to 1.61, P < 0.001; I2 = 70%) in NSCLC patients taking TKIs. Sensitivity analysis limited to studies including NSCLC with EGFR mutation showed consistent results (HR for PFS: 1.53, P=0.003; HR for OS: 1.43, P=0.001). Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, P for subgroup analysis all >0.05). Conclusions Concomitant use of AS in patients with NSCLC taking TKIs may be associated with poor survival outcomes.
Highlights
Background. e influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies
Inclusion criteria were (1) observational studies published as full-length articles; (2) included adult patients (18 years or above) with a confirmed diagnosis of NSCLC treated with EGFR-TKIs; (3) patients with concomitant use of AS, including pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), who considered as exposure; (4) compared progression-free survival (PFS) or overall survival (OS) between patients with and without concomitant use of AS; and (5) reported relative risk for the association between concomitant use of AS and survival outcomes in multivariate analysis including possible confounding factors. e definition of concomitant use of AS was consistent with the criteria adopted in the original articles
Results of Begg’s tests (P 0.34 and 0.77, respectively) and Egger’s regression tests (P 0.29 and 0.47, respectively) suggested the low risk of publication bias. In this meta-analysis, by pooling the results of available studies, we found that concomitant use of AS in NSCLC patients taking EGFR-TKIs was associated with worse PFS and OS as compared to those without AS
Summary
Background. e influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. E influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, P for subgroup analysis all >0.05). Erefore, we performed a meta-analysis to comprehensively summarize current evidence regarding the influence of concomitant AS on the survival of patients with NSCLC taking EGFR-TKIs. definition of concomitant AS use and number of AS users in each study; and (5) outcomes reported and variables adjusted in the multivariate model analyzing the association between concomitant AS use and survival outcomes. Definition of concomitant AS use and number of AS users in each study; and (5) outcomes reported and variables adjusted in the multivariate model analyzing the association between concomitant AS use and survival outcomes. e Newcastle–Ottawa Scale (NOS) [26] was used for study quality assessment, which included three domains such as defining of study groups, between-group comparability, and validation of the outcome. is scale totally scored from 1 to 9 stars, with 9 stars indicating the highest study quality level
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