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. 2022 Apr 29;12(1):7002.
doi: 10.1038/s41598-022-10938-x.

Proton pump inhibitors reduce the survival of advanced lung cancer patients with therapy of gefitinib or erlotinib

Chia-Han Lee #  1 , Mei-Chiou Shen #  2 , Ming-Ju Tsai  3   4 , Jung-San Chang  5   6 , Yaw-Bin Huang  1   2 , Yi-Hsin Yang  1   7 , Kun-Pin Hsieh  8   9
Affiliations

Proton pump inhibitors reduce the survival of advanced lung cancer patients with therapy of gefitinib or erlotinib

Chia-Han Lee et al. Sci Rep. .

Abstract

Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for advanced non-small-cell lung cancer. However, co-administration of either drug with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may reduce TKI's bioavailability. Therefore, we aimed to investigate the effects of these drug-drug interactions. We surveyed nationwide population-based databases between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced lung adenocarcinoma who received first-line gefitinib or erlotinib were identified. Effects on overall survival (OS) and time to next treatment (TTNT) association between PPIs or H2RAs and co-administrated gefitinib or erlotinib were evaluated. PPIs or H2RAs users were defined if the period overlapped with TKIs by ≥ 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. PPI group had the shortest median OS and TTNT compared to the H2RA and non-user groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P < 0.0001, TTNT: 8.47 vs. 10.78 vs. 10.33 months; P < 0.0001); (in erlotinib cohort: OS: 16.97 vs. 20.07 vs. 23.92 months; P < 0.0001, TTNT: 9.06 vs. 11.85 vs. 10.90 months; P = 0.0808). Compared with the non-user group, the adjusted hazard ratio (aHR) of the PPI group in the gefitinib was 1.58 on OS (95% CI 1.42-1.76), 1.37 on TTNT (95% CI 1.24-1.52); in the erlotinib was 1.54 on OS (95% CI 1.30-1.82) and 1.19 on TTNT (95% CI 1.01-1.39). Concurrent use of PPIs with first-line gefitinib or erlotinib therapy was associated with a worse OS and TTNT in patients with lung adenocarcinoma harboring EGFR mutations.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow chart of the study cohort.
Figure 2
Figure 2
Kaplan–Meier survival curves of overall survival (OS) between PPI and H2RA groups in gefitinib (A) and erlotinib (B); and time to next treatment (TTNT) between PPI and H2RA groups in gefitinib (C) and erlotinib (D).
Figure 3
Figure 3
Subgroup analysis: effects of different overlapping ratios in overall survival (OS) and time to next treatment (TTNT) between PPI and H2RA groups. (A) gefitinib cohort and (B) erlotinib cohort.
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