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

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. 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). 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). 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. Gastric/stomach cancer is the fifth most common cancer and the fifth main cause of cancer-related deaths globally. Gastric tumors led to 38,711 deaths in Japan in 2023, which is about 10% of all cancer deaths in Japan. The treatment options for advanced gastric cancer have previously been conventional chemotherapy with medicines such as fluorouracil, tegafur–gimeracil–oteracil, and cisplatin. However, a number of newer drugs have become available as initial (first-line) treatment for advanced gastric cancer in Japan. Some patients with advanced gastric cancer have a low amount of a certain protein, called human epidermal growth factor receptor 2 (HER2), and are considered to have HER2-negative gastric cancer. These patients do not typically respond to traditional anti-HER2 therapies. This study aimed to analyze the different treatment patterns and duration of therapy for HER2-negative advanced gastric cancer from 2012 to 2023 in everyday clinical practice in Japan. The study included 16,573 adult patients aged ≥ 20 years who received guideline-recommended first-line treatment for HER2-negative advanced gastric cancer from January 1, 2012 to December 31, 2023. Researchers found that newly recommended drugs were steadily introduced into Japanese clinical practice during the study period. The duration of therapy had gradually increased over time, as new drugs were introduced and used more broadly, including a first-line immunotherapy drug called nivolumab, when added to chemotherapy. Interestingly, the proportion of patients aged ≥ 75 years increased over time. These findings may guide further research to explore the optimal treatment sequence for patients with HER2-negative advanced gastric cancer.