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

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.