Stepwise prolongation of overall survival from first- to third-generation EGFR-tyrosine kinase inhibitors in non-small cell lung cancer and the prognostic impact of concomitant antacids.

530 Background: The introduction of new-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has afforded promising overall survival (OS) outcomes in clinical trials for non-small cell lung cancer (NSCLC). However, given the high cost associated with these agents, the extent of their adoption and the resulting impact on OS in real-world clinical settings remains uncertain. Concomitant use of antacids reportedly decreases the absorption of first-generation EGFR-TKIs, accompanied by a reduction in OS. Although concomitant antacids do not reduce the absorption of second- and third-generation EGFR-TKIs, the impact on OS remains unexplored. Methods: We conducted a nationwide retrospective cohort study utilizing data from the Tokushukai Real-world Data project and reviewed clinical data of consecutive patients with NSCLC who were treated with EGFR-TKIs between April 2010 and March 2020. Cox regression analyses were performed to examine the associations between OS and patient/tumor-related factors, hospital volume, hospital type, study period, and first-line EGFR-TKIs. Furthermore, we examined differences in OS between patients treated with and without concomitant antacids. Results: A total of 758 patients (58.5% females; median age, 73 years) were included. Over the study period, we noted increased utilization of osimertinib as the first-line EGFR-TKI. With a median follow up of 15.8 months, median OS was 28.4 months (95% confidence interval, 15.3–31.0). Age, body mass index, disease status, EGFR mutational status, and first-line EGFR-TKI were identified as significant prognostic factors. The 2-year OS rates for gefitinib, erlotinib, afatinib, and osimertinib were 70.1, 67.8, 75.6, and 90.8%, respectively. Low-volume hospitals showed a treatment transition to osimertinib over time and were non-inferior to high-volume hospitals in terms of the OS achieved. Patients administering gefitinib, erlotinib, afatinib, and osimertinib with concomitant antacids had lower OS values than those not taking concomitant antacids, with hazard ratios of 1.742, 1.329, 1.729, and 5.040, respectively. Conclusions: Our real-world data revealed that new-generation EGFR-TKIs could afford a prolonged OS irrespective of the volume and type of the hospital. Surprisingly, the concomitant antacid use was associated with poor OS in patients treated with osimertinib.