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+ 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.
Damato et al. (Thu,) studied this question.