Real-world treatment patterns and overall survival (OS) in patients (pts) with HER2-positive (HER2+) advanced or metastatic gastroesophageal adenocarcinomas (mGEA) in the US.

4053 Background: The first-line (1L) standard of care for pts with HER2+ mGEA is HER2-targeted therapy (HER2 Tx) plus platinum-based chemotherapy (CT). Recent immunotherapy (IO) addition to this regimen prolonged OS of pts with HER2+ programmed death-ligand 1 (PD-L1)-positive (PD-L1+) mGEA. Here, we describe real-world treatment patterns and OS in pts with HER2+ mGEA in the US since the FDA approval of 1L IO. Methods: Adults with HER2+ mGEA who initiated 1L systemic therapy between May 2021 and 2025 and had ≥6 mo of follow-up (or died within 6 mo) after 1L initiation, were identified from the Flatiron Health Electronic Health Records database. OS from 1L initiation was evaluated with the Kaplan-Meier method in the overall HER2+ cohort and in a subset of pts with PD-L1+ disease. Outcomes were also reported with HER2 Tx + CT ± IO use. Results: Of 2237 pts with known HER2 status prior to 1L therapy, 21% were HER2+, defined as immunohistochemistry (IHC) 3+, IHC 2+/ ERBB2 -amplified, or per physician’s note. Mean (SD) age was 66.1 (11.7), 20% of pts were female, and 66% had an Eastern Cooperative Oncology Group performance status ≤1. Of 292 pts with HER2+ mGEA and known PD-L1 status prior to 1L, 81% were PD-L1+ (combined positive score ≥1 or per physician’s note). Of the 467 pts with HER2+ mGEA who received 1L therapy, 60% had HER2 Tx, 28% had CT alone, and 10% received IO-based regimens without HER2 Tx. Of the 281 pts on 1L HER2 Tx, 58% had HER2 Tx + IO + CT and 37% had HER2 Tx + CT. Overall, 228/467 (49%) pts treated in the 1L went on to receive second-line (2L) therapy. In the 2L setting, 70% of pts received HER2 Tx, including 38% pts who only received CT or IO-based regimens without HER2 Tx in 1L treatment. A total of 42% of pts on 2L therapy received 1L and 2L HER2 Tx. Among the 467 pts with HER2+ mGEA, median OS (mOS) from 1L initiation was 17.4 mo. In the PD-L1+ subgroup, mOS was 19.0 mo in pts on HER2 Tx + IO + CT, and 17.2 mo in pts on HER2 Tx + CT without IO (Table). Across treatment groups, mOS remained <2 years, and the 24-mo OS rate was <40%. Conclusions: Despite the availability of HER2 Tx, a significant unmet need remains, as 40% of pts with HER2+ mGEA did not receive this option in 1L regimens. OS was numerically longer with HER2 Tx + IO + CT vs without IO in the HER2+/PD-L1+ mGEA subgroup. These data underscore the need to improve OS and the opportunity to enhance biomarker-guided management of HER2+ mGEA. OS analysis. HER2+ HER2+/PD-L1+ Subgroup HER2+ (Overall) 1L HER2 Tx + IO + CT 1L HER2 Tx + CT PD-L1+ (all) 1L HER2 Tx + IO + CT 1L HER2 Tx + CT (n = 467, 100%) (n = 164, 35%) (n = 103, 22%) (n = 237, 100%) (n = 95, 40%) (n = 40, 17%) Median OS, mo 17.4 19.3 17.2 17.2 19.0 17.2 (95% CI) (15.7, 20.5) (15.7, 22.3) (13.5, 21.3) (15.0, 20.9) (15.6, 24.6) (12.6, 24.4) OS Rate, (%) 6-mo 83.0 85.5 79.8 82.3 87.2 77.5 12-mo 65.5 67.6 66.4 64.1 67.9 66.2 18-mo 48.9 52.4 <jats:td colspan="1" rowspan="1