# Efficacy and safety of fruquintinib combined with albumin‐bound paclitaxel as second‐line therapy for advanced gastric cancer following failure of PD‐1 inhibitor‐containing treatment (TACTIC GC‐01): A phase II single‐arm study

## TL;DR

This study tested a combination of two drugs as a second-line treatment for advanced gastric cancer after immunotherapy, finding it effective with manageable side effects.

## Contribution

The study is the first to prospectively evaluate fruquintinib plus albumin-bound paclitaxel in PD-1 inhibitor-refractory gastric cancer.

## Key findings

- Median progression-free survival was 5 months and overall survival was 14 months.
- Objective response rate was 44.7% and disease control rate was 94.7%.
- Treatment-related adverse events occurred in 90.2% of patients, with 41.5% experiencing grade 3–4 events.

## Abstract

This study (TACTIC GC‐01) aimed to evaluate the efficacy and safety of fruquintinib combined with albumin‐bound paclitaxel as a second‐line treatment for advanced gastric cancer (GC) following progression on programmed cell death protein 1 (PD‐1) inhibitor‐based therapy. In this single‐center, single‐arm, prospective trial, patients with metastatic gastric adenocarcinoma who failed first‐line anti‐PD‐1 combined with chemotherapy treatment received six cycles of albumin‐bound paclitaxel combined with fruquintinib, followed by fruquintinib maintenance monotherapy. The primary endpoint was progression‐free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse event (AE) incidence. Between February 24, 2022, and March 26, 2024, 41 patients were enrolled, with three receiving only one treatment cycle. The safety analysis included all 41 patients, while the full analysis set comprised 38 patients. Median PFS and OS were 5 months and 14 months, respectively, with corresponding 6‐ and 12‐month PFS rates of 31.7% and 17.3%, and OS rates of 87.8% and 51.7%, respectively. Log‐rank analysis identified frontline immunotherapy duration (≥3 cycles) as a key risk factor for PFS, while metastasis to ≥2 organs significantly impacted OS. The ORR and DCR were 44.7% and 94.7%, respectively. Treatment‐related AEs occurred in 90.2% of patients, with grade 3–4 AEs (notably neutropenia and thrombocytopenia) observed in 41.5% of them. These findings suggest that fruquintinib plus albumin‐bound paclitaxel exhibits promising efficacy and manageable toxicity in anti‐PD‐1‐refractory GC, warranting further exploration in combination strategies targeting alternative pathways.

What's new?

Anti‐angiogenic drugs have shown promising efficacy as a second‐line treatment for advanced gastric cancer. However, it remains unclear how alterations in the tumor microenvironment following first‐line immunotherapy may impact tumor angiogenesis and influence subsequent therapeutic outcomes. This single‐arm study prospectively explored the efficacy and safety of the anti‐angiogenic drug fruquintinib combined with albumin‐bound paclitaxel as a second‐line treatment for gastric cancer after immunotherapy combined with chemotherapy. The results suggest that chemotherapy combined with anti‐angiogenic drugs can achieve good efficacy and manageable toxicity in an immunotherapy‐exposed population, potentially enriching the second‐line treatment landscape for patients with gastric cancer.