Kotani Daisuke, Yoshino Takayuki, Masuishi Toshiki, Sunakawa Yu, Takashima Atsuo, Yamazaki Kentaro, Kawakami Hisato, Nishina Tomohiro, Komatsu Yoshito, Esaki Taito, Eng Cathy, Ukrainskyj Stacey, Pallai Rajash, Nanda Shivani, Yang Zhao, Schelman William, Kania Marek, Satoh Taroh
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Department of Clinical Oncology, Aichi Cancer Center, Nagoya, Japan.
Int J Clin Oncol. 2025 Sep 1. doi: 10.1007/s10147-025-02852-9.
In the phase 3 FRESCO-2 study, fruquintinib plus best supportive care (BSC) significantly improved overall survival (OS) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). We present the results of a FRESCO-2 post hoc subgroup analysis evaluating outcomes of patients enrolled in Japan.
In FRESCO-2, patients had previously received all standard chemotherapies, anti-VEGF and anti-EGFR therapies if indicated, and had progressed on, or were intolerant to trifluridine-tipiracil and/or regorafenib. Patients were randomized 2:1 to receive fruquintinib 5 mg or matching placebo by mouth once daily on days 1-21 in 28-day cycles, plus BSC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and safety.
Of the 56 patients enrolled in Japan, 40 (71.4%) and 16 (28.6%) were randomized to fruquintinib and placebo, respectively. OS was improved with fruquintinib versus placebo (median 6.9 vs. 5.6 months; hazard ratio [HR], 0.42; 95% confidence interval [CI] 0.19 - 0.92). PFS was also improved with fruquintinib versus placebo (median 3.6 vs. 1.8 months; HR, 0.27; 95% CI 0.13 - 0.56). The incidence of grade ≥ 3 treatment-emergent adverse events (TEAEs) with fruquintinib versus placebo was 71.8% versus 29.4%; the most common grade ≥ 3 TEAEs with fruquintinib were hypertension (23.1%) and palmar-plantar erythrodysesthesia (17.9%).
Fruquintinib improved OS and PFS versus placebo in FRESCO-2 patients enrolled in Japan and demonstrated a manageable safety profile. Results from the Japan subgroup were consistent with the global FRESCO-2 population, thus supporting fruquintinib as a novel treatment option for patients in Japan with refractory mCRC.
ClinicalTrials.gov; NCT04322539.
在3期FRESCO-2研究中，与安慰剂加最佳支持治疗（BSC）相比，呋喹替尼加BSC显著改善了难治性转移性结直肠癌（mCRC）患者的总生存期（OS）。我们展示了一项FRESCO-2事后亚组分析的结果，该分析评估了日本入组患者的结局。
在FRESCO-2研究中，患者此前已接受了所有标准化疗，如有指征还接受了抗VEGF和抗EGFR治疗，并且已在曲氟尿苷-替匹嘧啶和/或瑞戈非尼治疗中进展或不耐受。患者按2:1随机分组，在28天周期的第1-21天每天口服一次5 mg呋喹替尼或匹配的安慰剂，加BSC。主要终点是OS；次要终点包括无进展生存期（PFS）和安全性。
在日本入组的56例患者中，分别有40例（71.4%）和16例（28.6%）被随机分配至呋喹替尼组和安慰剂组。与安慰剂相比，呋喹替尼改善了OS（中位值6.9个月对5.6个月；风险比[HR]，0.42；95%置信区间[CI] 0.19 - 0.92）。与安慰剂相比，呋喹替尼也改善了PFS（中位值3.6个月对1.8个月；HR，0.27；95% CI 0.13 - 0.56）。呋喹替尼组与安慰剂组≥3级治疗中出现的不良事件（TEAE）发生率分别为71.8%和29.4%；呋喹替尼组最常见的≥3级TEAE是高血压（23.1%）和手足红斑性感觉异常（17.9%）。
在日本入组的FRESCO-2患者中，与安慰剂相比，呋喹替尼改善了OS和PFS，并显示出可控的安全性。日本亚组的结果与全球FRESCO-2人群一致，因此支持呋喹替尼作为日本难治性mCRC患者的一种新的治疗选择。
ClinicalTrials.gov；NCT04322539。
