Concomitant Gastric Acid Suppressants on the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Meta-Analysis
Table 1
Characteristics of the included studies.
Study
Country
Design
Patient characteristics
Sample size
Mean age (years)
Male (%)
TKI used
Definition of AS use
Number of AS users
Outcomes and main results reported: HR (95% CI)
Variables adjusted
Hilton 2013
Canada
R
Advanced or metastatic NSCLC after standard chemotherapy had failed
485
62
65
Erlotinib
Self-reported PPIs or H2RAs users at baseline or during follow-up
190
PFS: 1.75 (1.43∼2.13), OS: 1.67 (1.34∼2.05)
Age, sex, PS, weight loss, time from diagnosis, response to prior therapy, histologic subtype, race, HGB, LDH, and current smoking
Chu 2015
Canada
R
Stage IIIB/IV NSCLC patients
544
64
50
Erlotinib
PPIs or H2RAs user confirmed by the database of prescription medications
124
PFS: 1.83 (1.48∼2.25), OS: 1.37 (1.11∼1.69)
Age, sex, PS, and histologic subtype
Zenke 2016
Japan
R
Patients with advanced NSCLC with EGFR mutations
130
64
37
Erlotinib or gefitinib
Medical records approved users of PPIs or H2RAs
47
PFS: 1.15 (0.73∼1.79), OS: 1.41 (0.83∼2.35)
Age, sex, PS, smoking, prior therapy, and bone metastasis
Kumarakulasinghe 2016
Singapore
R
Patients with advanced NSCLC with EGFR mutations
157
62
53
Erlotinib or gefitinib
Medical records approved users of PPIs or H2RAs
55
PFS: 1.37 (0.89∼2.12), OS: 1.47 (0.92∼2.35)
Age, sex, race, PS, CCI, smoking, brain and liver metastasis
Chen 2016
China
R
Patients with advanced NSCLC with EGFR mutations
269
65
42
First-generation EGFR-TKIs
Medical records approved users of PPIs or H2RAs
57
For PPIs: PFS: 1.42 (0.81∼2.49), OS: 2.27 (1.26∼4.11); for H2RAs: PFS: 1.19 (0.55∼2.57), OS: 1.46 0.92∼2.33);
Age, sex, DM, smoking, PS, histologic type, and bone, liver, or pleura metastasis
Sedano 2018
Spain
R
Stage III/IV NSCLC patients
163
70
64
Erlotinib or gefitinib
Medical records approved users of PPIs or H2RAs
118
PFS: 2.5 (1.61∼3.88)
Age, sex, PS, and treatment line
Sharma 2019
US
R
Old NSCLC patients
7448
76
48
Erlotinib
PPIs user confirmed by the database of prescription medications
1616
OS: 1.11 (1.02∼1.20)
Age, sex, and comorbidities
Fang 2019
China
R
NSCLC patients
1278
NR
36
Gefitinib
PPIs user confirmed by the database of prescription medications
309
OS: 1.67 (1.33∼2.09)
Age, sex, comorbidities, and income
Kwok 2020
China
R
Advanced lung AC with EGFR mutations
193
68
28
Gefitinib
Medical records approved users of PPIs or H2RAs
61
For PPIs: PFS: 3.38 (2.18∼5.25), OS: 2.52 (1.67∼3.79); for H2RAs: PFS: 2.27 (1.54∼3.52), OS: 1.30 (0.74∼2.62);
Age, sex, smoking, primary EGFR mutation and presence of brain metastasis
Guo 2020
China
R
Stage IIIB/IV NSCLC patients
188
61
42
Gefitinib
Medical records approved users of PPIs or H2RAs
49
PFS: 1.33 (0.78∼1.98)
Age, sex, PS, EGFR mutation, cancer stage, and brain metastasis
Su 2020
China
R
Stage IIIB/IV NSCLC patients with EGFR mutations
853
66
36
Gefitinib, erlotinib, and afatinib
Medical records approved users of PPIs or H2RAs
92
OS: 1.01 (0.75∼1.36)
Age, sex, PS, smoking, clinical stage, previous therapy, CCI, and histologic type
Patients with advanced NSCLC with EGFR-activating mutations
235
64
37
Dacomitinib
Medical records approved users of PPIs
83
PFS: 1.24 (0.84∼1.81), OS: 1.04 (0.70∼1.55)
Age, sex, race, baseline BW, PS, smoking, EGFR mutation type, number of target lesions, and organs with metastases
Li 2021b
US
R
Patients with advanced NSCLC with EGFR-activating mutations
229
63
42
Gefitinib
Medical records approved users of PPIs
70
PFS: 1.13 (0.80∼1.59), OS:1.31 (0.89∼1.93)
Age, sex, race, baseline BW, PS, smoking, EGFR mutation type, number of target lesions, and organs with metastases
The study by Li et al. (2021) included two cohorts using dacomitinib or gefitinib, respectively, and these two datasets were included independently. TKI, tyrosine kinase inhibitor; AS, acid suppressants; R, randomized; NSCLC, non-small-cell lung cancer; AC, adenocarcinoma; EGFR, epithelial growth factor receptor; PPIs, proton pump inhibitors; H2RAs, histamine type-2 receptor antagonists; PFS, progression-free survival; OS, overall survival; PS, performance status; HGB, hemoglobin; LDH, lactate dehydrogenase; CCI, Charlson Comorbidity Index; BW, body weight; DM, diabetes mellitus.
