FRESCO-2: A Global Phase III Study Investigating the Efficacy and Safety of Fruquintinib in Metastatic Colorectal Cancer

Dasari, Arvind; Sobrero, Alberto; Yao, James C.; Yoshino, Takayuki; Schelman, William R.; Zhao, Yong; Chien, Caly; Kania, Marek; Tabernero, Josep; Eng, Cathy

doi:10.2217/fon-2021-0202

Cited by 27 publications

(10 citation statements)

References 47 publications

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“…A total of 687 patients with progression on or intolerance to trifluridine-tipiracil and/or regorafenib and previously treated with chemotherapy will be randomized to either fruquintinib or placebo in conjunction with best supportive care. This study will determine the OS and PFS and provide valuable insights into a diverse population ( 59 ).…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review

Xu¹,

Yu²,

Liu³

et al. 2022

Transl Cancer Res TCR

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Objective: The efficacy and safety of regorafenib and fruquintinib are studied extensively in different populations and trials across the world to determine their potential benefits. Here we review the efficacy and safety of regorafenib and fruquintinib as third-line treatment option for colorectal cancer (CRC).Background: CRC is the third most prevalent cancer worldwide, but the optimal third-line treatment option is still debatable. Regorafenib is a multikinase inhibitor that inhibits several cell signaling receptors, including vascular endothelial growth factor receptors (-1, -2, and -3) (VEGFRs), platelet-derived growth factor (PDGF), fibroblast growth factor, epidermal growth factor (EGF), angiotensin II, and Rapidly Accelerated Fibrosarcoma kinase pathway. On the other hand, fruquintinib inhibits signaling through the VEGFRs family. Regorafenib and fruquintinib have both received United States Food and Drug Administration (USFDA) approval for treating metastatic CRC (mCRC) in patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and Rat sarcoma wild type, an anti-EGF receptor therapy.Methods: A review of literature was conducted in PubMed and Embase with the keywords "regorafenib" OR "fruquintinib" AND "colorectal cancer" for clinical studies performed in randomized controlled settings and real-world settings.Conclusions: Regorafenib and fruquintinib are effective and well tolerated options for the third-line treatment of patients with CRC. Both have a similar survival outcome with Regorafenib showing a slightly better toxicity profile.

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Section: Methodsmentioning

confidence: 99%

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review

Xu¹,

Yu²,

Liu³

et al. 2022

Transl Cancer Res TCR

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“…In a randomized, multicenter, phase III FRESCO trial conducted in China (NCT02314819), fruquintinib treatment in patients with mCRC who progressed after standard second-line therapy showed significant improvement in the PFS and OS [ 111 ]. Furthermore, in a randomized phase III FRESCO-2 trial (NCT04322539), with a total of 687 patients with refractory mCRC for more than third-line treatment, fruquintinib treatment showed significant PFS and OS [ 112 ]. These results indicate the clinical benefit of Fruquintinib for the patients with mCRC beyond third-line therapy.…”

Section: Vegf/vegfr Targeting Strategymentioning

confidence: 99%

Current Targeted Therapy for Metastatic Colorectal Cancer

Ohishi

Kaneko

Yoshida³

et al. 2023

IJMS

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Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab, were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

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“…Fruquintinib 9, was designed to be highly selective on small-molecule tyrosine kinase inhibitor of VEGF receptors (VEGFRs)-1, -2, and -3, it has been approved and relied in China by NMPA for the treatment of metastatic colorectal cancer. Currently, fruquintinib is being studied in patients with refractory metastatic colorectal cancer as part of a Phase III study (Dasari, Sobrero et al 2021).…”

Section: Pyrimidine Derivatives As Vegfr Inhibitors In Clinical Trialsmentioning

confidence: 99%

Review on the Significance of Pyrimidine Derivatives as Potent Anti-Angiogenic Vegfr-2 Inhibitors

Issa

Saleh

Khalifa

et al. 2023

Al-Azhar Journal of Pharmaceutical Sciences

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Cancer is a disease in which human cells grow uncontrollably and spread to other body parts. Cancer is the second leading cause of death globally and accounted for 9.6 million deaths in 2022 according to the statistics of the World Health Organization. Cancer can begin in any part of the human organs when the normal cell loses the ability to control the division cycle, which may inhibit apoptosis. Cancer cells grow and multiply by activating the angiogenetic factors to build new capillaries that can supply tumor tissue with nutrients. Cancerous tumors spread into or invade nearby tissues and can travel to other organs in the body to form new carcinogenic tissue by metastasis. The goal of treatment is control growth of cancer cells, and induction the programmed cell death. Pyrimidines and its derivatives have been found as effective and valuable pharmacophoric units in medicinal chemistry to design and develop a wide range of bioactive compounds. The present review summarizes the advances in lead compounds of pyrimidines hybrids and their related heterocycles in the treatment of cancer. Moreover, the review also helps to intensify the drug development process by providing an understanding of the potential role of these hybridized pharmacophoric features as VEGFR-2 inhibitors. Abbreviations Abbreviation Meaning FGFR1Fibroblast growth factor receptor 1 VEGFR Vascular Endothelial Growth Factor CSF-1RColony stimulating factor 1 receptor NETs Neuroendocrine tumors AKT Protein kinase B (PKB), also known as Akt A549Human lung adenocarcinoma cell line MCF-7Human breast cancer cell line HepG2Human liver cancer cell line Ovcar-3High-grade serous ovarian adenocarcinoma cell line ObjectivesThe aim of this study is to highlight the role of Pyrimidines containing compounds in inhibiting VEGFR-2 as well as to suggest some new aspects of treatment of cancer using pyrimidines scaffold soon.

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FRESCO-2: A Global Phase III Study Investigating the Efficacy and Safety of Fruquintinib in Metastatic Colorectal Cancer

Cited by 27 publications

References 47 publications

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review

Current Targeted Therapy for Metastatic Colorectal Cancer

Review on the Significance of Pyrimidine Derivatives as Potent Anti-Angiogenic Vegfr-2 Inhibitors

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