Fruzaqla (fruquintinib)

Over the past decade, regorafenib and trifluridine-tipiracil were the only available drugs and often provided limited clinical benefit compared to best supportive care. Results from subsequent practice-changing trials opened several novel therapeutic avenues, both for unselected patients (such as trifluridine-tipiracil plus bevacizumab or fruquintinib) and for subgroups defined by the presence of actionable alterations in their tumours (such as HER2-targeted therapies or KRASG12C inhibitors) or with no acquired mechanisms of resistance to the previously received targeted agents in circulating tumour DNA (such as retreatment with anti-EGFR antibodies). In this Review, we provide a comprehensive overview of advances in the field over the past few years and offer a practical perspective on translation of the most relevant results into the daily management of patients with metastatic colorectal cancer using an evidence-based algorithm. Finally, we discuss some of the most appealing ongoing areas of research and highlight approaches with the potential to further expand the therapeutic armamentarium.

P2, N=30, Not yet recruiting, Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital; Fujian Cancer Hospital

P2, N=58, Not yet recruiting, Xuancheng People's Hospital; Xuancheng People's Hospital of Anhui Province

P1/2, N=62, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=67, Recruiting, Hebei Medical University Fourth Hospital

Finally, the reliability of the model was also verified through the risk classification using the nomogram. We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug.

Therefore, this article conducts a systematic review encompassing the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of fruquintinib. Through this review, we aimed to offer a reference for the clinical application and subsequent development of fruquintinib.

P1, N=129, Completed, Hutchison Medipharma Limited | Active, not recruiting --> Completed

P=N/A, N=30, Recruiting, Ningbo Medical Center Lihuili Hospital

P2, N=29, Active, not recruiting, Wuhan Union Hospital, China | Not yet recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=39, Not yet recruiting, The First Hospital of Lanzhou University; The First Hospital of Lanzhou University

P2, N=40, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

The real-world efficacy and safety of fruquintinib in advanced CRC patients are numerically superior to that in the previous phase III studies. SMI, brain metastasis and CEA could serve as potential markers for patient selection.

P3, N=412, Not yet recruiting, Hutchmed

However, its use is associated with significant bleeding risks, including rare but severe complications such as cerebellar hemorrhage. This case report presents a patient with mCRC who developed a cerebellar hemorrhage shortly after initiating fruquintinib therapy, highlighting the need for careful patient monitoring and individualized risk assessment to mitigate such serious adverse events.

P4, N=78, Not yet recruiting, Takeda

P=N/A, N=28, Not yet recruiting, Fudan University

P2, N=68, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

A budget impact model was developed to compare two scenarios: a reference scenario in which patients received regorafenib, trifluridine/tipiracil, or trifluridine/tipiracil with bevacizumab and an alternative scenario in which patients received reference scenario treatments or fruquintinib. PMPM costs from the Medicare perspective were greater than the base-case (commercial) ($0.17 vs. $0.07) due to higher incidence of CRC in that population. Fruquintinib is associated with a low budget impact for payers based on proposed thresholds in the US.

Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.

These data demonstrate that F consistently improved OS vs P in pts with previously treated mCRC with and without liver mets at baseline. F is an effective and tolerable treatment option for pts with mCRC regardless of liver mets.

P=N/A, N=40, Recruiting, Xiantao First People's Hospital; Xiantao First People's Hospital

P2, N=75, Recruiting, Suining Central Hospital; Suining Central Hospital

P3, N=430, Not yet recruiting, Chipscreen Biosciences, Ltd.

P2, N=0, Withdrawn, Sun Yat-sen University | N=12 --> 0 | Trial completion date: Jan 2026 --> Jul 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2023 --> Jul 2025

P1/2, N=25, Not yet recruiting, Wuhan Union Hospital, China

P=N/A, N=70, Not yet recruiting, Wuhan University

P=N/A, N=70, Not yet recruiting, Wuhan University

P2, N=158, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=36, Not yet recruiting, Sun Yat-sen University

P2/3, N=132, Not yet recruiting, Peking University Cancer Hospital & Institute

P2/3, N=84, Recruiting, Sun Yat-sen University

In the multicenter, double-blind phase 3 FRUTIGA trial, 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma who progressed on fluorouracil- and platinum-containing chemotherapy were randomized (1:1) to receive fruquintinib (an inhibitor of vascular endothelial growth factor receptor-1/2/3; 4 mg orally, once daily) or placebo for 3 weeks, followed by 1 week off, plus paclitaxel (80 mg/m2 intravenously on days 1/8/15 per cycle). Fruquintinib plus paclitaxel as a second-line treatment significantly improved PFS, but not OS, in Chinese patients with advanced gastric or gastroesophageal junction adenocarcinoma and could potentially be another treatment option for these patients. ClinicalTrials.gov registration: NCT03223376 .

P2, N=66, Recruiting, West China Hospital

P2, N=129, Not yet recruiting, Fudan University

P=N/A, N=60, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P3, N=300, Enrolling by invitation, BeiGene | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Aug 2024 --> Dec 2026

P3 | "In the heavily pretreated pt population of FRESCO-2, the number of metastatic sites and time from diagnosis of metastasis to randomization are important prognostic factors. In pts with more indolent or more aggressive disease, F was effective in improving OS, PFS, and delay to PS deterioration vs P."

P2, N=40, Recruiting, Fudan University

P3 | "In the FRESCO-2 trial, F + BSC demonstrated a clinically meaningful quality-adjusted survival benefit compared with P + BSC in heavily pretreated patients with refractory mCRC. Clinical trial information: NCT04322539."

P3 | "In FRESCO, eligible pts had received ≥2 prior chemotherapy regimens and were permitted to have received prior anti-VEGF and/or anti-EGFR therapies, whereas in FRESCO-2, in addition to standard chemotherapies, anti-VEGF, and anti-EGFR therapies if indicated, prior exposure to trifluridine/tipiracil (TAS) and/or regorafenib (rego) was required. F is effective in mCRC with a manageable safety profile regardless of prior TAS or rego tx and sequence. Improvement with F was similar for OS and PFS despite the number and sequence of prior regimens. F provides a new tx option for pts with previously treated mCRC regardless of prior TAS or rego exposure."

P4, N=51, Active, not recruiting, Zhongnan Hospital | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Jan 2025