MAIC of Fruquintinib Plus Paclitaxel Versus Ramucirumab Plus Paclitaxel in Advanced G/GEJ Adenocarcinoma

Adjusted Indirect Treatment Comparison of Fruquintinib-based Therapy Versus Standard Care in Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: A MAIC Analysis.

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Gastroesophageal Junction Adenocarcinoma; Advanced Gastric Cancer; Ramucirumab; Fruquintinib
• Intervention / Treatment: Drug: Fruquintinib+Paclitaxel; Drug: Ramucirumab+Paclitaxel

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: 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)

• Study Type: Observational
• Enrollment (Estimated): 1143

Contacts and Locations

• Study Contact: Name: Feng Wang; Phone Number: 020-8734-3571; Email: wangfeng@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fruquintinib + paclitaxel; Group 1: Fruquintinib + Paclitaxel (IPD)	Drug: Fruquintinib+Paclitaxel; (using IPD from the FRUTIGA trial, n=703) Fruquintinib：subjects received Fruquintinib orally, once daily for 3 wks on/ 1 wk off Paclitaxel：Paclitaxel 80mg/㎡ at day 1,8,15 of 4-week cycle.; Other Names: HMPL-013+paclitaxel
Ramucirumab + paclitaxel; Group 2: Control Therapy (AgD from RAINBOW-Asia)	Drug: Ramucirumab+Paclitaxel; (using published AgD from RAINBOW-Asia, n=440) Ramucirumab：8 milligrams/kilogram (mg/kg) intravenous (IV) infusion on Days 1 and 15 of every 4-week cycle Paclitaxel ：Paclitaxel 80mg/㎡ at day 1,8,15 of 4-week cycle.; Other Names: LY3009806 +paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from randomization to progression/death, assessed via weighted Cox model	about 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	CR+PR per RECIST 1.1, compared via weighted logistic regression	about 3 years
Disease Control Rate (DCR)	CR+PR+SD≥6 weeks, analyzed via weighted proportions	about 3 years
Overall Survival (OS)	Time from randomization to death, analyzed using weighted Kaplan-Meier	about 3 years
PFS by ECOG, metastasis burden, primary site, etc	To examine the associations between subgroup factors (including ECOG, metastasis burden, primary site, etc) and Progression-Free Survival (PFS).	about 3 years
OS by ECOG, metastasis burden, primary site, etc	To examine the associations between subgroup factors (including ECOG, metastasis burden, primary site, etc) and Overall Survival (OS).	about 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity Analyses：Progression-Free Survival (PFS)	Simulated Treatment Comparison (STC), Bootstrap confidence intervals (100 iterations)	about 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Feng Wang, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): September 5, 2025
• Primary Completion (Estimated): August 5, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 5, 2025
• First Submitted That Met QC Criteria: August 20, 2025
• First Posted (Estimated): August 28, 2025

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: HMPL-013-FLAG-G118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Within 6 months after main publication.
• IPD Sharing Access Criteria: Secondary analysis generated by our team require approval by an independent review committee and a signed data use agreement.
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No