Adjusted Indirect Treatment Comparison of Fruquintinib-based Therapy Versus Standard Care in Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: A MAIC Analysis.
Conditions: Advanced Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Fruquintinib, Ramucirumab
Sponsor: Sun Yat-sen University

FRUIT-MAIC 
Version 
1.0 
Date 
1st August 2025 
Brief Title 
Match-Adjusted Indirect Comparison (MAIC) of Fruquintinib plus Paclitaxel versus Ramucirumab 
plus Paclitaxel in Advanced Gastric/GEJ Adenocarcinoma 
Acronym 
FRUIT-MAIC 
Sponsor 
 
Information provided by 
 
Brief Summary 
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). 
Detailed Description 
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:  
o 
Seven prognostic factors balanced: age <65, male sex, ECOG 0, GEJ primary, peritoneal 
metastases, metastatic sites, prior doublet chemotherapy 
o 
Optimization via BFGS algorithm (convergence tolerance 1e-6) 
o 
Effective sample size (ESS) retention: > 50% 
• 
Statistical Analysis: 
o 
Primary: Adjusted PFS hazard ratio (HR) using Bucher method with 95% bootstrap CI 
(100 iterations) 
o 
Secondary: Weighted Cox models for OS; logistic regression for ORR/DCR 
o 
Sensitivity: Simulated Treatment Comparison (STC) and covariate threshold analyses 
• 
Sensitivity Analyses: 
o 
RMST analyses were conducted as supportive evidence alongside primary Cox models for 
time-to-event endpoints violating proportional hazards assumptions. 
o 
Restricted mean survival time (RMST) 
o 
Simulated Treatment Comparison (STC) 
o 
Bootstrap confidence intervals (100 iterations) 
Official Title 
Adjusted Indirect Treatment Comparison of Fruquintinib-based Therapy Versus Standard Care in 
Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: A MAIC Analysis. 
Conditions 
• 
Advanced Gastric Cancer 
• 
Gastroesophageal Junction Adenocarcinoma 
Intervention/Treatment 
Experimental: Fruquintinib + paclitaxel, Ramucirumab + paclitaxel 
Common comparator: Placebo + paclitaxel (weighted FRUTIGA and RAINBOW-Asia reference arm) 
Inclusion Criteria 
1. Histologically confirmed gastric/GEJ adenocarcinoma 
2. Advanced or metastatic disease 
3. ECOG 0-1 
4. Received either fruquintinib + paclitaxel or reference regimen 
5. Available baseline characteristics for matching variables 
Exclusion Criteria 
1. Missing key outcome data 
2. Incomplete baseline characteristics for >2 matching variables 
3. Prior fruquintinib exposure (control arm only) 

Primary Purpose 
Treatment Comparison 
Allocation 
Observational  
Interventional Model 
Indirect Treatment Comparison 
Masking 
 
Participant Group/Arm 
Group 1: Fruquintinib + Paclitaxel (IPD) 
Group 2: Control Therapy (AgD from RAINBOW-Asia) 
Intervention/Treatment 
 
 
 
Primary Outcome Measures  
Outcome Measure 
Measure Description 
Time Frame 
Progression-Free Survival 
(PFS) 
Time from randomization to progression/death, 
assessed via weighted Cox model 
per FRUTIGA trial data cutoff 
 
Second Outcome Measures  
Outcome Measure 
Measure Description 
Time Frame 
Objective Response Rate 
(ORR) 
CR+PR per RECIST 1.1, compared via weighted 
logistic regression 
per FRUTIGA trial data cutoff 
Disease Control Rate 
(DCR) 
CR+PR+SD≥6 weeks, analyzed via weighted 
proportions 
per FRUTIGA trial data cutoff 
Overall Survival (OS) 
Time from randomization to death, analyzed using 
weighted Kaplan-Meier 
per FRUTIGA trial data cutoff 
Subgroup Analyses 
PFS/OS by ECOG, metastasis burden, primary site, 
etc. 
As per primary outcomes 
 
 
 
 
 
 
 
 
 
 
Other Outcome Measures  
Outcome Measure 
Measure Description 
Time Frame 
Progression-Free Survival 
(PFS) 
Simulated Treatment Comparison (STC), Bootstrap 
confidence intervals (100 iterations) 
per FRUTIGA trial data cutoff