4.5 Review

The Management of Unresectable, Advanced Gastrointestinal Stromal Tumours

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Review Oncology

The management of metastatic GIST: current standard and investigational therapeutics

Ciara M. Kelly et al.

Summary: GIST is the most common mesenchymal tumor of the gastrointestinal tract, with KIT or PDGFR alpha mutations playing a key role in its development. Imatinib has revolutionized the management of GIST as first line treatment, but patients often experience disease progression after a few years of therapy. New treatment options are being explored for imatinib-refractory GIST.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study

Yoon-Koo Kang et al.

Summary: Avapritinib, a potent inhibitor of KIT and PDGFRA mutant kinases, showed clinical activity in GISTs with specific mutations. The VOYAGER study comparing avapritinib and regorafenib in advanced GIST patients did not find a significant difference in median progression-free survival, but showed similar overall survival and safety profiles between the two treatments.

JOURNAL OF CLINICAL ONCOLOGY (2021)

Article Oncology

Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study

John R. Zalcberg et al.

Summary: This study reports the efficacy and safety of ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.d. after progressive disease (PD) among patients randomized to ripretinib 150 mg QD in the INVICTUS study. The findings suggest that ripretinib IPDE may provide additional clinical benefit with acceptable safety profile in this patient population.

ONCOLOGIST (2021)

Article Oncology

Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors A Phase 1b/2a Nonrandomized Clinical Trial

Andrew J. Wagner et al.

Summary: In this non-randomized phase 1b/2a clinical trial, the type I and type II KIT inhibitors PLX9486 and sunitinib were safely coadministered at recommended doses in patients with refractory GIST, suggesting that targeting two complementary conformational states of the same kinase was associated with clinical benefit.

JAMA ONCOLOGY (2021)

Review Gastroenterology & Hepatology

Ripretinib for the treatment of advanced gastrointestinal stromal tumor

John R. Zalcberg

Summary: GISTs are rare tumors of the gastrointestinal tract driven by mutations in the KIT and/or PDGFRA genes, with TKIs revolutionizing their treatment. Ripretinib, a novel TKI, has shown significant improvements in progression-free survival and overall survival in patients with advanced GIST in clinical trials, leading to its approval for adult patients who have received multiple TKIs.

THERAPEUTIC ADVANCES IN GASTROENTEROLOGY (2021)

Review Oncology

Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward

M. Julia Lostes-Bardaji et al.

Summary: GIST serves as a paradigm for targeted inhibition of oncogenic driver mutations in cancer, with Ripretinib emerging as a new standard of care for advanced, multi-resistant GIST patients. This recent approval by the FDA marks a major breakthrough in sarcoma drug development after nearly a decade without new treatment approvals in GIST.

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Article Oncology

Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit inPatients WithRefractory Gastrointestinal Stromal Tumors A Phase 1b/2a Nonrandomized Clinical Trial

Andrew J. Wagner et al.

Summary: In a clinical trial, combining type I and type II KIT inhibitors PLX9486 and sunitinib showed promising efficacy and safety in treating advanced GIST, suggesting that targeting two complementary conformational states of the same kinase may lead to clinical benefit with acceptable safety profile.

JAMA ONCOLOGY (2021)

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Secondary KIT mutations: the GIST of drug resistance and sensitivity

Andrea Napolitano et al.

BRITISH JOURNAL OF CANCER (2019)

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Gastrointestinal stromal tumors: a comprehensive review

Trisha M. Parab et al.

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Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene

Valentina Indio et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

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Gastrointestinal Stromal Tumors: The GIST of Precision Medicine

Lin Mei et al.

TRENDS IN CANCER (2018)

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Gastrointestinal stromal tumors (GISTs): point mutations matter in management, a review

Peter J. Oppelt et al.

JOURNAL OF GASTROINTESTINAL ONCOLOGY (2017)

Review Radiology, Nuclear Medicine & Medical Imaging

Imaging therapy response of gastrointestinal stromal tumors (GIST) with FDG PET, CT and MRI: a systematic review

Antonia Dimitrakopoulou-Strauss et al.

CLINICAL AND TRANSLATIONAL IMAGING (2017)

Review Endocrinology & Metabolism

Paraganglioma and phaeochromocytoma: from genetics to personalized medicine

Judith Favier et al.

NATURE REVIEWS ENDOCRINOLOGY (2015)

Review Oncology

Inhibition of HSP90 molecular chaperones: moving into the clinic

Rocio Garcia-Carbonero et al.

LANCET ONCOLOGY (2013)

Review Oncology

Gastrointestinal stromal tumours: origin and molecular oncology

Christopher L. Corless et al.

NATURE REVIEWS CANCER (2011)

Article Oncology

Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors

Narasimhan P. Agaram et al.

GENES CHROMOSOMES & CANCER (2008)

Article Oncology

Molecular correlates of imatinib resistance in gastrointestinal stromal tumors

Michael C. Heinrich et al.

JOURNAL OF CLINICAL ONCOLOGY (2006)

Review Medical Laboratory Technology

KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)

Jerzy Lasota et al.

SEMINARS IN DIAGNOSTIC PATHOLOGY (2006)

Article Medicine, General & Internal

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

SG O'Brien et al.

NEW ENGLAND JOURNAL OF MEDICINE (2003)

Article Medicine, General & Internal

Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors

GD Demetri et al.

NEW ENGLAND JOURNAL OF MEDICINE (2002)

Article Genetics & Heredity

Familial paraganglioma and gastric stromal sarcoma: A new syndrome distinct from the Carney triad

JA Carney et al.

AMERICAN JOURNAL OF MEDICAL GENETICS (2002)

Article Medicine, General & Internal

Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor.

H Joensuu et al.

NEW ENGLAND JOURNAL OF MEDICINE (2001)

Article Pathology

KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors

ML Lux et al.

AMERICAN JOURNAL OF PATHOLOGY (2000)