Real-world biomarker testing rates, targeted therapy use, and clinical outcomes in patients with advanced gastric or GEJ cancer in the United States.

Abstract

e16039 Background: Guidelines endorse testing patients (pts) with advanced (adv) gastric cancer (GC) or gastroesophageal junction cancer (GEJC) for HER2, PD-L1, MMR/MSI, and CLDN18 to guide first-line (1L) treatment (tx) decisions. Tx decisions in cases of multiple targets are not well defined in real-world (rw) practice. This study evaluated the alignment between biomarker results and rw-1L tx and its association with clinical outcomes. Methods: This retrospective cohort study of adult pts with adv GC/GEJC used the US-based, electronic health record (EHR)-derived deidentified Flatiron Health Research Database. Pt follow-up started from the first EHR activity after January 1, 2011, and spanned to September 30, 2025. Pts were included if they received 1L tx on or after September 1, 2017. Biomarker testing was assessed before and up to 30d post 1L start. 1L regimens included immunotherapy (IO) + chemotherapy (Chemo) + HER2, IO + Chemo, HER2, Chemo, and Other. Pts were further categorized into received “guideline concordant tx” or not according to biomarker test results and 1L tx received. Cox proportional hazard models estimated time to next tx or death (rwTTNTD) associated with guideline concordance tx, adjusting for demographics, clinical characteristics, and biomarker results. To account for non-proportional hazards, a piecewise Cox model with a time split at 20 months was used. Results: Of 3,828 pts (58% GC, 42% GEJC, 60% ≥65 years, 57% diagnosis stage IV/IVB), testing rates for HER2, MMR/MSI, PD-L1, and CLDN18 were 78%, 58%, 50%, and 6%, with positivity rates of 17%, 7%, 66%, and 47%, respectively. 13.4% (n = 322) of pts tested for > 2 biomarkers had > 2 actionable biomarkers (eg, HER2+ & PD-L1+). Concordance between biomarker status and 1L tx was high for HER2+ disease, with 62% of HER2+ pts receiving HER2-directed therapy. In contrast, concordance was lower for PD-L1+ and CLDN18+ disease, with < 37% of pts receiving IO or targeted tx in concordance with each positive biomarker. Among pts with ≥2 actionable biomarkers, IO therapy was not prioritized as consistently as HER2-directed therapy (32% received IO + Chemo + HER2, 34% HER2, 34% other tx groups). Pts receiving non-concordant tx had a 16% increased risk of next tx or death during the first 20 months after 1L start vs pts receiving concordant tx (HR [95% CI], 1.16 [1.07-1.26]); P < .001). No significant association was observed beyond 20 months (0.76 [0.55-1.04]). HER2+ status was independently associated with reduced risk (0.85 [0.76-0.95]; P = .003). Conclusions: In rw-practice, tx decisions were more often discordant with biomarker results for PD-L1+ or CLDN18+ compared with HER2+. Concordant first-line tx showed an early rwTTNTD benefit without sustained risk reduction after about 20 months. Broader biomarker testing and clearer tx-prioritization frameworks are needed to advance precision medicine in adv GC and GEJC.