Advanced Gastric Cancer, Fruquintinib, Gastroesophageal Junction Adenocarcinoma, Ramucirumab
Conditions
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: 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)
Interventions
(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.
DRUGRamucirumab+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.
Sponsors
Sun Yat-sen University
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | about 3 years | Time from randomization to progression/death, assessed via weighted Cox model |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | about 3 years | CR+PR per RECIST 1.1, compared via weighted logistic regression |
| Disease Control Rate (DCR) | about 3 years | CR+PR+SD≥6 weeks, analyzed via weighted proportions |
| PFS by ECOG, metastasis burden, primary site, etc | about 3 years | To examine the associations between subgroup factors (including ECOG, metastasis burden, primary site, etc) and Progression-Free Survival (PFS). |
| OS by ECOG, metastasis burden, primary site, etc | about 3 years | To examine the associations between subgroup factors (including ECOG, metastasis burden, primary site, etc) and Overall Survival (OS). |
| Overall Survival (OS) | about 3 years | Time from randomization to death, analyzed using weighted Kaplan-Meier |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity Analyses：Progression-Free Survival (PFS) | about 3 years | Simulated Treatment Comparison (STC), Bootstrap confidence intervals (100 iterations) |
Contacts
Primary ContactFeng Wang
Outcome results
None listed