Abstract
Fruquintinib has recently been introduced as a later-line treatment option for unresectable or recurrent colorectal cancer (CRC) in Japan. However, real-world evidence from Japanese clinical practice remains limited; therefore, we evaluated the efficacy and safety of fruquintinib in Japanese patients with unresectable or recurrent CRC. This multicentre retrospective study was conducted at 23 institutions in Japan. Patients who received fruquintinib monotherapy between November 2024 and July 2025 were included. The primary endpoint was real-world progression-free survival (rwPFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), relative dose intensity, and safety. Of the 185 enrolled patients, 171 were included in the analysis. The median rwPFS and OS periods were 2.5 and 5.8 months, respectively, and the DCR was 38.1%; these effectiveness outcomes were numerically less favourable than those reported in FRESCO-2. Liver and peritoneal metastases and hypoalbuminaemia were associated with poorer outcomes. Initial dose reduction was independently associated with shorter rwPFS but not with OS. Treatment-emergent adverse events (TEAEs) occurred in 95.9% of the patients and grade ≥3 TEAEs occurred in 49.1%. Proteinuria was the most frequent adverse event and the leading cause of treatment modification. Baseline hypertension was associated with a higher incidence of proteinuria. Fruquintinib demonstrated modest real-world activity with no new safety signals in Japanese clinical practice. However, proteinuria frequently led to treatment modification, highlighting the importance of careful toxicity management and sustained treatment continuity to maximise clinical benefit.