REPERTOIRE: Real-world treatment (tx) patterns and outcomes in US patients (pts) with HER2-negative (HER2-) advanced gastric, gastroesophageal junction and esophageal adenocarcinoma (GC/GEJC/EAC).

306 Background: GC/GEJC/EAC is often diagnosed at an advanced stage, where there are limited tx options, particularly upon first-line (1L) progression and in pts who are HER2-. Evidence describing real-world tx patterns and clinical outcomes after recent approvals for immunotherapies (IOs; e.g. nivolumab) is sparse. This study describes the change in tx paradigms, biomarker testing, and outcomes after the approval of IOs in 2021. Methods: This retrospective, observational study used Flatiron Health’s US electronic health records, mostly sourced from community clinics. We included adult pts with metastatic, recurrent or unresectable HER2- GC/GEJC/EAC with 1L tx from 1 Jan 2016 to 30 Apr 2024. Baseline characteristics and txs from 1L to 3L were summarized. Overall survival (OS) was reported by line of therapy. All analyses were stratified by 1L start date (pre- vs post-2021) to assess changes since IO approval. Results: In total, 2200 pts met the selection criteria (1253 pre- and 947 post-2021); 55.8% were diagnosed as Stage IV and 20.7% had prior surgery. Among pts with 1L tx: 38.2% died, 43.6% received 2L tx, 12.9% were censored and 5.4% had no further treatment; only 17.6% received 3L tx. Pre-2021, 25.6% of pts received PD-L1 testing. Post-2021, 61.4% of pts received testing. Overall, 61.5% of pts had a PD-L1 combined positive score ≥1. Pre-2021, FOLFOX was the most common 1L tx overall (41.0%), while the most common 2L tx was paclitaxel + ramucirumab (23.0%). After 2021, FOLFOX remained the most frequent 1L tx (25.7%) while FOLFOX + nivolumab was given to 22.3% of pts as 2L tx, vs 19.8% of pts who were given paclitaxel + ramucirumab. Pembrolizumab use in 2L declined from 18.7% pre-2021 to 6.1% post-2021. Pre-2021, median OS from 1L tx was 9.5 (8.9–10.3) months; post-2021 it was 12.3 (11.2–13.5) months. With 2L tx pre-2021, median OS was 6.8 (5.7–7.2) months; post-2021 it was 8.6 (6.5–10.5) months. Conclusions: Post-2021, IO uptake was gradual and although PD-L1 testing rates increased, they remained sub-optimal. Despite numerical improvements after IO approval in 2021, median OS remains poor for advanced HER2- GC/GEJC/EAC pts, especially in 2L settings. As most pts do not have the opportunity to receive 3L tx, newer therapeutic options should be initiated as early as possible. More effective personalized or biomarker-based txs are needed. Pre-2021(n=1253) Post-2021(n=947) Total(n=2200) Most common 1L txs, n (%) Fluorouracil + leucovorin + oxaliplatin (FOLFOX) 514 (41.0) 243 (25.7) 757 (34.4) Carboplatin + paclitaxel 226 (18.0) 167 (17.6) 393 (17.9) FOLFOX + nivolumab 3 (0.2) 225 (23.8) 228 (10.4) Most common 2L txs, n (%) n=600 n=359 n=959 Paclitaxel + ramucirumab 138 (23.0) 71 (19.8) 209 (21.8) Pembrolizumab 112 (18.7) 22 (6.1) 134 (14.0) FOLFOX 92 (15.3) 10 (2.8) 102 (10.6) FOLFOX + nivolumab 10 (1.7) 80 (22.3) 90 (9.4)