FRESCO-2: A global Phase 3 multi-regional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer
FRESCO-2研究: 一项旨在评估呋喹替尼用于治疗难治性转移性结直肠癌患者的疗效和安全性的全球 III 期国际多中心临床试验
|报告人：||Arvind Dasari, MD, MS, Associate Professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX|
|会议环节：||Proffered Paper session 2: GI, lower digestive|
|日期和时间：||2022年9月12日（星期一）巴黎时间上午10:55 – 11:15|
|地点：||7.2.F – Fécamp Auditorium|
Effective treatment options are limited for patients (pts) with refractory metastatic colorectal cancer (mCRC). Fruquintinib (F), a highly selective, potent, oral tyrosine kinase inhibitor of VEGFR-1, -2, and -3, was approved in China in the 3L+ mCRC setting based on results from the FRESCO trial (NCT02314819). FRESCO-2 (NCT04322539) evaluated F in more heavily pre-treated pts reflecting current global practices.
FRESCO-2 was a randomized, double-blind, placebo (P)-controlled, phase 3 MRCT conducted in the US, Europe, Japan & Australia, comparing F + best supportive care (BSC) with P + BSC. F or P was given 5 mg PO, QD, 3 wks on, 1 wk off, in 28-d cycles. Key criteria: Prior chemotherapy, anti-VEGF therapy, and, if RAS wild type (WT), anti-EGFR therapy; if BRAFV600E mutant (MT) or MSI-H, ≥1 targeted regimen; & prior exposure to trifluridine/tipiracil (T) and/or regorafenib (R). Pts were randomized 2:1 to F + BSC or P + BSC and stratified by: prior therapy T, R or both; RAS status (WT, MT) & duration of metastatic disease (≤18, >18 months [m]). The primary endpoint was overall survival (OS). Key secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) & safety. Final analysis was after 480 OS events.
From 2Sep2020 to 14Dec2021, 691 pts were randomized; F:461 vs P:230. Baseline characteristics were balanced. F significantly improved OS (median: 7.4 m vs 4.8 m P; HR=0.66; [95% CI: 0.55, 0.80]; p<0.001) & PFS (median: 3.7 m vs 1.8 m P; HR=0.32; [95% CI: 0.27, 0.39]; p<0.001). The median duration of follow-up was 11.3 m F vs 11.2 m P. Subsequent anti-cancer therapies were 29.4% F vs 34.3% P. DCR was 55.5% F vs 16.1% P & ORR was 1.5% F vs 0% P. Grade ≥3 adverse events were 62.7% F vs 50.4% P; those occurring in ≥5% on F were hypertension (13.6% vs 0.9% P), asthenia (7.7% vs 3.9% P) & hand-foot syndrome (6.4% vs 0% P).
F had a significant and clinically meaningful improvement in OS in pts with refractory mCRC. F was well tolerated, with a safety profile consistent with the established profile for F monotherapy. FRESCO-2 results are consistent with FRESCO and should support a new treatment option in refractory mCRC.