Clinical improvement and rapid radiographic regression induced by a MET inhibitor in a patient with MET-amplified glioblastoma.

S, Abinav Sivashankar; Kwak, E. L.; Clark, J. W.; Wang, D. L.; Louis, D. N.; Iafrate, A. John; Batchelor, T.

doi:10.1200/jco.2011.29.15_suppl.2072

Cited by 12 publications

(7 citation statements)

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“…Although comprehensive clinical data are lacking to support its efficacy in treating MET -driven NSCLC, a recent case report72 has demonstrated a rapid and durable response to crizotinib in an NSCLC patient with de novo MET amplification and lacking an ALK rearrangement. While this report only represents one patient, the findings are intriguing and suggest that crizotinib may be effective in MET -amplified NSCLC, as has been shown for other MET -amplified cancers 73,74…”

Section: Crizotinib For Other Mutations (Ros1 and Met)mentioning

confidence: 56%

Clinical use of crizotinib for the treatment of non-small cell lung cancer

Roberts¹

2013

BTT

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Discoveries over the last decade have fundamentally transformed the way we define lung cancer. Gone are the days of the simple binary classification system of non-small cell lung cancer (NSCLC) and small cell lung cancer. Today, accurate identification of the histological and molecular subtype of NSCLC is required for selecting standard cytotoxic chemotherapy and targeted therapies. The identification of anaplastic lymphoma kinase (ALK) rearrangements in 5–7% of NSCLC patients and the rapid clinical development of crizotinib for these patients is the most recent clinical example necessitating the proper identification of the molecular characteristics of NSCLC for treatment decisions. The discovery of ALK rearrangements in NSCLC serendipitously coincided with the development of crizotinib for other ALK or MET driven malignancies. The clinical development of crizotinib for ALK-positive NSCLC patients has been an amazing success story of translational medicine that relied on the prior clinical experience of other targeted predecessors (i.e. erlotinib in EGFR mutant NSCLC) and a compound ready for clinical development to gain expedited FDA approval. This review discusses the clinical development and use of crizotinib in NSCLC.

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Section: Crizotinib For Other Mutations (Ros1 and Met)mentioning

confidence: 56%

Clinical use of crizotinib for the treatment of non-small cell lung cancer

Roberts¹

2013

BTT

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“…However, in a recent case report, a NSCLC patient with de novo MET amplification but no ALK rearrangement achieved a rapid and durable response to crizotinib, indicating that it is also a bona fide MET inhibitor clinically. 64 Dramatic clinical improvement and radiographic regression were also observed in patients with MET-amplified esophagogastric adenocarcinoma 65 and glioblastoma multiforme 66 upon treatment with crizotinib.…”

Section: Crizotinib (Pf-2341066 Pfizer)mentioning

confidence: 95%

MET Signaling: Novel Targeted Inhibition and Its Clinical Development in Lung Cancer

Yan

Thiagarajan

Patrick

2012

Journal of Thoracic Oncology

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MET is a versatile receptor tyrosine kinase within the human kinome which is activated by its specific natural ligand hepatocyte growth factor (HGF). MET signaling plays an important physiologic role in embryogenesis and early development, whereas its deregulation from an otherwise quiescent signaling state in mature adult tissues can lead to upregulated cell proliferation, survival, scattering, motility and migration, angiogenesis, invasion, and metastasis in tumorigenesis and tumor progression. Studies have shown that MET pathway is activated in many solid and hematological malignancies, including lung cancer, and can be altered through ligand or receptor overexpression, genomic amplification, MET mutations, and alternative splicing. The MET signaling pathway is known to be an important novel target for therapeutic intervention in human cancer. A number of novel therapeutic agents that target the MET/HGF pathway have been tested in early-phase clinical studies with promising results. Phase 3 studies of MET targeting agents have just been initiated. We will review the MET signaling pathway and biology in lung cancer and the recent clinical development and advances of MET/HGF targeting agents with emphasis on discussion of issues and strategies needed to optimize the personalized therapy and further clinical development.

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“…Once the maximal tolerated dose has been reached and the recommended Phase II dose determined from the first part of A8081001, it is planned to enroll 25 patients with tumors that harbor MET amplification or mutations. Crizotinib has demonstrated clinical activity in MET -amplified NSCLC,42 MET -amplified gastroesophageal carcinoma,43 and MET- amplified glioblastoma 44. Additionally, because of the evolutionary relatedness between ALK and ROS receptor tyrosine kinases,45 crizotinib has also been shown in vitro to be a potential ROS inhibitor 46.…”

Section: Other Targets Of Crizotinibmentioning

confidence: 99%

“…Crizotinib has demonstrated clinical activity in MET -amplified NSCLC, 42 MET -amplified gastroesophageal carcinoma, 43 and MET- amplified glioblastoma. 44 Additionally, because of the evolutionary relatedness between ALK and ROS receptor tyrosine kinases, 45 crizotinib has also been shown in vitro to be a potential ROS inhibitor. 46 The current amendment to A8081001 allows for screening and testing of crizotinib in tumors with ROS rearrangement.…”

Section: Other Targets Of Crizotinibmentioning

confidence: 99%

Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged nonsmall cell lung cancer and beyond

Ou¹

2011

DDDT

161

134

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Epidermal growth factor receptor (EGFR) tyrosine inhibitors were first approved for the treatment of non-small cell lung cancer (NSCLC) in 2003 in the US. Activating EGFR mutations were subsequently discovered in 2004, and heralded the era of molecular targeted therapy in NSCLC. The discovery of anaplastic lymphoma kinase (ALK) rearrangement in NSCLC in 2007 by two independent groups not only represents the first time ALK rearrangement has been discovered in common solid tumors but also represents another important milestone in the era of molecular targeted therapy in NSCLC. Crizotinib, a mesenchymal-epithelial transition (MET)/ALK multi-targeted receptor tyrosine kinase inhibitor went into early Phase I clinical development in 2007. Using the knowledge that NSCLC patients with activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors, crizotinib was rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC, based on a break apart fluorescence in situ hybridization assay, developed by two of the crizotinib Phase I sites. It cumulated in the conditional approval of crizotinib by the US Food and Drug Administration on August 26, 2011 for the treatment of ALK-rearranged NSCLC. The conditional approval was based on response rates of 50% and 61% from 255 ALK-rearranged NSCLC patients enrolled in two single-arm trials. Common adverse events of crizotinib include mild transient visual disorders, mild gastrointestinal toxicities, fatigue, rare alanine transaminase elevations, and even rarer pneumonitis (1.6%). Confirmatory trials comparing crizotinib with standard chemotherapy are ongoing. It took an unprecedented four years from the discovery of ALK rearrangement in NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the treatment of ALK-rearranged NSCLC.

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Clinical improvement and rapid radiographic regression induced by a MET inhibitor in a patient with MET-amplified glioblastoma.

Cited by 12 publications

References 0 publications

Clinical use of crizotinib for the treatment of non-small cell lung cancer

Clinical use of crizotinib for the treatment of non-small cell lung cancer

MET Signaling: Novel Targeted Inhibition and Its Clinical Development in Lung Cancer

Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged nonsmall cell lung cancer and beyond

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