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

Sun Yat-sen University

Status: Not yet enrolling

Conditions: Ramucirumab; Gastroesophageal Junction Adenocarcinoma; Fruquintinib; Advanced Gastric Cancer

Treatments: Drug: Ramucirumab+Paclitaxel; Drug: Fruquintinib+Paclitaxel

Study type: Observational

Funder types: Other

Identifiers

NCT07144995

HMPL-013-FLAG-G118

Details and patient eligibility

About

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).

Full 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)

Enrollment: 1,143 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

1,143 participants in 2 patient groups

Fruquintinib + paclitaxel

Description:

Group 1: Fruquintinib + Paclitaxel (IPD)

Treatment:

Drug: Fruquintinib+Paclitaxel

Ramucirumab + paclitaxel

Description:

Group 2: Control Therapy (AgD from RAINBOW-Asia)

Treatment:

Drug: Ramucirumab+Paclitaxel