Infigratinib in Patients with Recurrent Gliomas and <i>FGFR</i> Alterations: A Multicenter Phase II Study

Lassman, Andrew B.; Sepúlveda‐Sánchez, Juan Manuel; Cloughesy, Timothy F.; Gil-Gil, Miguel; Puduvalli, Vinay K.; Raizer, Jeffrey J.; Vos, Filip Y.F. De; Wen, Patrick Y.; Butowski, Nicholas; Clément, Paul M.; Groves, Morris D.; Belda-Iniesta, Cristóbal; Giglio, Pierre; Soifer, Harris S.; Rowsey, Steven; Xu, Cindy; Avogadri, Francesca; Ge, Wei; Moran, Susan; Roth, Patrick

doi:10.1158/1078-0432.ccr-21-2664

Cited by 60 publications

(37 citation statements)

References 34 publications

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“… 227 However, infigratinib had limited efficacy in patients with recurrent gliomas and different FGFR genetic alterations. 228 A phase I trial (NCT01004224) demonstrated antitumor activity of infigratinib for FGFR1‐amplified squamous cell NSCLC and FGFR3‐mutant bladder/urothelial cancers. 229 The three approved FGFR inhibitors are also under evaluation in breast cancer, bladder cancer, prostate cancer, myeloid/lymphoid neoplasms, and NSCLC and in combination with PD‐1 monoclonal antibody for advanced solid tumors (NCT03238196, NCT04917809, NCT04754425, NCT03011372, NCT05210946, and NCT03547037).…”

Section: Selective Small Molecule Kinase Inhibitorsmentioning

confidence: 99%

“…Erdafitinib manifested clinical improvement with stable disease and minor response for glioblastoma patients with FGFR3‐TACC3 rearrangements 227 . However, infigratinib had limited efficacy in patients with recurrent gliomas and different FGFR genetic alterations 228 . A phase I trial (NCT01004224) demonstrated antitumor activity of infigratinib for FGFR1‐amplified squamous cell NSCLC and FGFR3‐mutant bladder/urothelial cancers 229 .…”

Section: Selective Small Molecule Kinase Inhibitorsmentioning

confidence: 99%

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Small molecule inhibitors targeting the cancers

Liu

Chen

Zhang

et al. 2022

MedComm

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Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

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Section: Selective Small Molecule Kinase Inhibitorsmentioning

confidence: 99%

Section: Selective Small Molecule Kinase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors targeting the cancers

Liu

Chen

Zhang

et al. 2022

MedComm

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“…FGFR and TACC-alterations are present in a subgroup of glioblastoma [38]. The most common aberrations occur in receptor FGFR1 and FGFR3 in about 8% of all gliomas [38,39]. Infigratinib is a strong ATP-competitive FGFR1-3selective tyrosine kinase inhibitor that can be used for the treatment of patients with FGFR-driven conditions [40].…”

Section: Inhibition Of Fibroblast Growth Factor Receptor (Fgfr) Infig...mentioning

confidence: 99%

New therapeutic strategies based on molecularly targeted therapy in glioblastoma – a case report and review of the literature

Szklener

Anna

Kuryło

et al. 2022

Current Issues in Pharmacy and Medical Sciences

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Glioblastomas are the most common and most lethal forms of malignant primary brain tumor. We present a case report of a patient with III-grade glioma who achieved stable disease (SD) and clinical improvement after trametinib administration. We also report a review of the literature to Current Treatment Guidelines of Glioblastoma and new therapeutic strategies based on molecularly targeted therapy. Traditional treatments, including surgery, radiotherapy, and chemotherapy, have many limitations concerning the prognosis of patients with glioblastomas. Unfortunately, these tumors’recur after primary resection in the majority of cases. There is no standard therapy for recurrence of GBM. Targeted therapy offers a promising new treatment strategy. Regardless of those outstanding results much more can be done in the field of therapeutic options. Most urgent concerns include potent combining molecular targeted therapy with other types of treatments, selecting a group of patients for whom they turn out to be the most beneficial, and addressing adverse events of these molecules.

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“…The FGFR1-3 receptor inhibitors AZ4547 and BGJ398 were both evaluated for patients with FGFR1-TACC1 and FGFR3-TACC3 fused glioblastomas (NCT028224133 and NCT01975701); however, the results have not yet been published. A study considering infigratinib (BGJ398) for patients with unselected FGFR-altered glioblastoma proved the safety of the drug, despite only limited effects [ 99 ]. Nevertheless, response with a stable disease for over one year was observed in a patient with a FGFR3-TACC3-fused glioblastoma [ 99 ].…”

Section: Fgfr3-tacc3-fusions: a New Hope For Targeted Therapy?mentioning

confidence: 99%

“…A study considering infigratinib (BGJ398) for patients with unselected FGFR-altered glioblastoma proved the safety of the drug, despite only limited effects [ 99 ]. Nevertheless, response with a stable disease for over one year was observed in a patient with a FGFR3-TACC3-fused glioblastoma [ 99 ].…”

Section: Fgfr3-tacc3-fusions: a New Hope For Targeted Therapy?mentioning

confidence: 99%

FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma

Gött

Uhl

2022

IJMS

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Oncogenic fusion genes have emerged as successful targets in several malignancies, such as chronic myeloid leukemia and lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein—FGFR3-TACC3 fusion—is prevalent in 3–4% of human glioblastoma. The fusion protein leads to the constitutively activated kinase signaling of FGFR3 and thereby promotes cell proliferation and tumor progression. The subgroup of FGFR3-TACC3 fusion-positive glioblastomas presents with recurrent clinical and histomolecular characteristics, defining a distinctive subtype of IDH-wildtype glioblastoma. This review aims to provide an overview of the available literature on FGFR3-TACC3 fusions in glioblastoma and possible implications for actual clinical practice.

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Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study

Cited by 60 publications

References 34 publications

Small molecule inhibitors targeting the cancers

Small molecule inhibitors targeting the cancers

New therapeutic strategies based on molecularly targeted therapy in glioblastoma – a case report and review of the literature

FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma

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