Evolution of Real-World Treatment Patterns over Time in Patients with HER2-Negative Advanced Gastric Cancer: A Retrospective Database Cohort Study from Japan.

INTRODUCTION: The treatment paradigm for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (aGC) has shifted after the introduction of new regimens. METHODS: This retrospective analysis of hospital-based administrative claims data included adults (aged ≥ 20 years) who received guideline-recommended first-line treatment for HER2-negative aGC from January 1, 2012 to December 31, 2023. The primary objective was to examine the evolution of real-world treatment patterns in these patients across six eras, each spanning two calendar-year intervals from 2012 to 2023 (era 1, 2012-2013; era 2, 2014-2015; era 3, 2016-2017; era 4, 2018-2019; era 5, 2020-2021; era 6, 2022-2023). RESULTS: Among 16,573 patients (72.1% male, 27.9% female; median age 70 years), tegafur-gimeracil-oteracil (S-1) plus cisplatin (SP) was the most common first-line regimen in 2012-2013 (94.0%). S-1 plus oxaliplatin (SOX) use increased from 22.4% in 2014-2015 to 66.3% in 2020-2021. Capecitabine plus oxaliplatin (CapeOX) and folinic acid-fluorouracil plus oxaliplatin (FOLFOX) use also increased in 2020-2021 (to 6.0% and 10.5%, respectively), whereas SP decreased (to 14.8%). In 2022-2023, first-line nivolumab plus chemotherapy (SOX, FOLFOX, or CapeOX) became the most common regimens (48.1%, 11.0%, and 2.6%, respectively), while SOX and SP decreased (to 26.2% and 2.0%, respectively). The proportion of patients aged ≥ 75 years increased over time. Median overall duration of therapy (DoT) also increased from 2012-2013 (8.5 months) to 2022-2023 (12.5 months). DoT did not change in the second- and third-line setting. In 2022-2023, median first-line DoT was longer with nivolumab plus chemotherapy versus chemotherapy alone (6.3 vs 5.0 months). CONCLUSION: Use of newly introduced first-line regimens for HER2-negative aGC in Japanese clinical practice has increased over time, with an increase in the overall DoT.