# Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial.

**Tumor:** Cáncer gástrico/UGE
**Autores:** Meng X, Yang D, Liu Y et al
**Revista:** Front Immunol (2025)
**PMID:** 40799651 | **PMCID:** PMC12339537
**DOI:** [10.3389/fimmu.2025.1638316](https://doi.org/10.3389/fimmu.2025.1638316)
**Fuente:** PubMed Central (open access)

## Relevancia
Cáncer gástrico/UGE tratado con quimioterapia perioperatoria (FLOT/MAGIC) o inmunoterapia: documenta downstaging ganglionar, valor pronóstico de ypN0 y rendimiento ganglionar tras NAC. Comparable al paradigma mamario: ypN0 tras quimioterapia neoadyuvante es marcador pronóstico fuerte y guía la linfadenectomía D2.

## Abstract
Locally advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma faces high recurrence risks despite radical surgery. Perioperative chemotherapy (e.g., FLOT regimen) improves survival but has limited pathological complete response (pCR) rates and significant toxicity. Immunotherapy and anti-angiogenic agents show promise in advanced G/GEJ cancer. This trial evaluates fruquintinib (a VEGFR-1/2/3 inhibitor), sintilimab (PD-1 inhibitor), and SOX (oxaliplatin+S-1) as perioperative therapy for resectable locally advanced G/GEJ adenocarcinoma.

This prospective, single-arm, phase II trial (N = 25) enrolls treatment-na&#xef;ve adults (18-75 years) with histologically confirmed, resectable cT3-4aN+M0 G/GEJ adenocarcinoma (AJCC 8th edition). Patients receive 3 cycles of neoadjuvant therapy:Fruquintinib:4 mg orally, days 1-14 (21-day cycle). S-1: 80-120 mg orally twice daily (based on BSA), days 1-14. Oxaliplatin: 130 mg/m&#xb2; IV, day 1. Sintilimab: 200 mg IV, day 1.Radical gastrectomy with D2 lymphadenectomy follows 4-6 weeks post-neoadjuvant therapy. Adjuvant therapy (3 cycles of sintilimab for pCR patients; 3 cycles of preoperative regimen for non-pCR) starts 4-6 weeks post-surgery. Endpoints: Primary: pCR rate (ypT0/Tis ypN0 per CAP criteria). Secondary: R0 resection rate, major pathological response (MPR, &#x2264;10% residual tumor), 2-year event-free survival (EFS), 2-year overall survival (OS), safety (NCI CTCAE v5.0). Exploratory: Biomarker analysis of tumor microenvironment. Statistical Analysis: Sample size (25 patients) was calculated using Fisher's exact test (one-sided &#x3b1; = 0.05, power = 80%), assuming pCR improvement from 5% (historical control) to 20%. Efficacy analyses use intention-to-treat (ITT) population; safety analyses include patients receiving &#x2265;1 neoadjuvant dose.

This is the first trial combining fruquintinib, sintilimab, and SOX in perioperative G/GEJ cancer. If successful, it may expand treatment options for locally advanced disease. Limitations include single-arm design and small sample size.

Chinese Clinical Trial Registry (ChiCTR2400084194).

## Acceso
Disponible en PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC12339537/

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*Datos de PubMed. Citar: doi 10.3389/fimmu.2025.1638316*
