# Treatment and Outcomes in Advanced Gastroesophageal Adenocarcinoma in the Pre-Immunotherapy Era Based on the Spanish AGAMENON-SEOM Registry

## TL;DR

This study compares treatment and survival outcomes for HER2-negative and HER2-positive advanced gastric/gastroesophageal junction cancer patients in Spain before immunotherapy was available.

## Contribution

The study highlights the survival gap between HER2-negative and HER2-positive patients and emphasizes the need for targeted therapies in the HER2-negative group.

## Key findings

- HER2-negative patients had shorter progression-free and overall survival compared to HER2-positive patients.
- Most HER2-positive patients received trastuzumab as part of first-line treatment.
- Approximately 70% of patients with advanced G/GEJa were HER2-negative.

## Abstract

There is an unmet need for targeted therapy for human epidermal growth factor receptor 2–negative (HER2-negative), locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (advanced G/GEJa), which is associated with poor survival outcomes. This study aimed to describe the characteristics, treatment, and survival of HER2-negative and HER2-positive patients with advanced G/GEJa in Spain. Among 1357 patients from the Spanish AGAMENON-SEOM registry who initiated first-line polychemotherapy for advanced G/GEJa between 2015 and 2019 (inclusive), 70.1% had HER2-negative disease. Overall, 56.3% of patients with advanced G/GEJa received only one line of therapy, and most (92.7%) HER2-positive patients received targeted therapy (trastuzumab) as part of first-line treatment. HER2-negative patients had significantly shorter progression-free survival (median of 5.92 months vs. 7.37 months) and overall survival (median of 10.49 months vs. 13.82 months) compared with HER2-positive patients. The survival difference underscores the critical need for targeted first-line therapies for HER2-negative patients.

Background/Objectives: Human epidermal growth factor receptor 2–negative (HER2-negative), locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (advanced G/GEJa) is associated with poor survival outcomes, and there is an unmet need for targeted therapy. This study, conducted in the pre-immunotherapy era, aimed to describe the characteristics and management, and compare the survival, of HER2-negative and HER2-positive patients initiating first-line (1L) treatment for advanced G/GEJa in Spain and estimate the number of HER2-negative patients eligible for 1L polychemotherapy. Methods: Patients from the AGAMENON-SEOM registry who initiated 1L polychemotherapy for advanced G/GEJa (2015–2019) in Spain were included. Results: In total, 1357 patients were included (951 [70.1%] HER2-negative; 315 [23.2%] HER2-positive; 91 [6.7%] unknown HER2 status). Most patients (56.3%) received one line of therapy; 27.6% received two lines; and 16.1% received three lines. Among HER2-positive patients, 92.7% received trastuzumab as part of 1L treatment. The use of FOLFOX and CAPOX increased over the study period (2015–2019). HER2-negative patients had significantly shorter progression-free survival (median, 5.92 months [95% CI, 5.59–6.38] vs. 7.37 months [95% CI, 6.55–8.29]; log-rank p < 0.0001) and overall survival (median, 10.49 months [95% CI, 9.74–11.05] vs. 13.82 months [95% CI, 12.30–14.74]; adjusted time ratio, 0.812 [95% CI, 0.722–0.913]; p = 0.0005) than HER2-positive patients. Per probabilistic sensitivity analyses, an estimated 2856 (95% CI, 1619–4134) Spanish patients with HER2-negative advanced G/GEJa were eligible for 1L polychemotherapy in 2024. Conclusions: The survival difference between HER2-positive and HER2-negative patients underscores the critical need for targeted therapies for HER2-negative patients in the 1L setting.