This anchored matching-adjusted indirect comparison (MAIC) evaluates the relative efficacy of fruquintinib-paclitaxel (using IPD from the FRUTIGA trial, n=703) versus ramucirumab-paclitaxel (using published AgD from RAINBOW-Asia, n=440) in advanced gastric/GEJ adenocarcinoma. Baseline characteristics are adjusted via entropy balancing weights. Primary endpoint is progression-free survival (PFS) analyzed by Bucher method; secondary endpoints include overall survival (OS) and objective response rate (ORR). Sensitivity analyses comprise restricted mean survival time (RMST) analysis and simulated treatment comparison (STC).

This retrospective MAIC analysis employs individual patient data (IPD) from the FRUTIGA trial (fruquintinib arm) and published aggregate data (AgD) from RAINBOW-Asia (ramucirumab arm), with placebo as the common anchor. Pseudo individual participant data (Pseudo-IPD) for the RAINBOW-Asia trial were reconstructed from published Kaplan-Meier curves using the Guyot algorithm (2012).

•Weighting Methodology: Seven prognostic factors balanced: age <65, male sex, ECOG 0, GEJ primary, peritoneal metastases, metastatic sites, prior doublet chemotherapy Optimization via BFGS algorithm (convergence tolerance 1e-6) Effective sample size (ESS) retention: > 50%

•Statistical Analysis: Primary: Adjusted PFS hazard ratio (HR) using Bucher method with 95% bootstrap CI (100 iterations) Secondary: Weighted Cox models for OS; logistic regression for ORR/DCR Sensitivity: Simulated Treatment Comparison (STC) and covariate threshold analyses

•Sensitivity Analyses: RMST analyses were conducted as supportive evidence alongside primary Cox models for time-to-event endpoints violating proportional hazards assumptions.

Restricted mean survival time (RMST) Simulated Treatment Comparison (STC) Bootstrap confidence intervals (100 iterations)

Inclusion Criteria:

• Histologically confirmed gastric/GEJ adenocarcinoma
• Advanced or metastatic disease
• ECOG 0-1
• Received either fruquintinib + paclitaxel or reference regimen
• Available baseline characteristics for matching variables

Exclusion Criteria:

• Missing key outcome data
• Incomplete baseline characteristics for >2 matching variables
• Prior fruquintinib exposure (control arm only)

This retrospective MAIC analysis employs individual patient data (IPD) from the FRUTIGA trial (fruquintinib arm) and published aggregate data (AgD) from RAINBOW-Asia (ramucirumab arm), with placebo as the common anchor.

This study utilizes aggregated data from published literature and de-identified IPD authorized by Hutchison Medipharma Limited. Secondary analysis generated by our team will be shared.

Within 6 months after main publication.

Secondary analysis generated by our team require approval by an independent review committee and a signed data use agreement.