Gastrointestinal stromal tumors, version 2.2014: Featured updates to the NCCN Guidelines

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

[1]  J. Crowley,et al.  Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  S. Hirota,et al.  Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. , 1998, Science.

[3]  J. Blay,et al.  Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. , 2009, European journal of cancer.

[4]  J. Blay,et al.  Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  G. Demetri,et al.  Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. , 2013, The Lancet. Oncology.

[6]  J. Blay,et al.  Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. , 2010, The Lancet. Oncology.

[7]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[8]  C. Antonescu,et al.  Acquired Resistance to Imatinib in Gastrointestinal Stromal Tumor Occurs Through Secondary Gene Mutation , 2005, Clinical Cancer Research.

[9]  P. Marynen,et al.  Activity of Dasatinib, a Dual SRC/ABL Kinase Inhibitor, and IPI-504, a Heat Shock Protein 90 Inhibitor, against Gastrointestinal Stromal Tumor–Associated PDGFRAD842V Mutation , 2008, Clinical Cancer Research.

[10]  M. von Mehren,et al.  A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  N. Socci,et al.  SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors , 2012, BMC Cancer.

[12]  Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Fletcher,et al.  Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  K. Owzar,et al.  Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Y. Kakeji,et al.  Phase 2 study of nilotinib as third‐line therapy for patients with gastrointestinal stromal tumor , 2011, Cancer.

[16]  H. Joensuu,et al.  Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. , 2009, European journal of cancer.

[17]  G. Demetri,et al.  Amulticenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors ( GIST ) following failure of at least imatinib and sunitinib , 2013 .

[18]  H. Chang,et al.  Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs) , 2008, Journal of surgical oncology.

[19]  P Reichardt,et al.  Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  Narasimhan P. Agaram,et al.  Mechanisms of Sunitinib Resistance in Gastrointestinal Stromal Tumors Harboring KITAY502-3ins Mutation: An In vitro Mutagenesis Screen for Drug Resistance , 2009, Clinical Cancer Research.

[21]  C. Antonescu,et al.  Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations , 2010, Proceedings of the National Academy of Sciences.

[22]  Xin Huang,et al.  Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial , 2006, The Lancet.

[23]  J. Blay,et al.  Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial , 2013, The Lancet.

[24]  Yan Zhang,et al.  KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients , 2009, Proceedings of the National Academy of Sciences.

[25]  E. Wardelmann,et al.  Polyclonal Evolution of Multiple Secondary KIT Mutations in Gastrointestinal Stromal Tumors under Treatment with Imatinib Mesylate , 2006, Clinical Cancer Research.

[26]  J. Blay,et al.  Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  M. van Glabbeke,et al.  Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. , 2004, European journal of cancer.

[28]  S. Hirota,et al.  Sunitinib-resistant gastrointestinal stromal tumors harbor cis-mutations in the activation loop of the KIT gene , 2009, International Journal of Clinical Oncology.

[29]  C. Antonescu,et al.  Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  C. Antonescu,et al.  NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. , 2010, Journal of the National Comprehensive Cancer Network : JNCCN.

[31]  P. Engstrom,et al.  Evaluation of nilotinib in advanced GIST previously treated with imatinib and sunitinib , 2011, Cancer Chemotherapy and Pharmacology.

[32]  A. D. Van den Abbeele,et al.  Clonal Evolution of Resistance to Imatinib in Patients with Metastatic Gastrointestinal Stromal Tumors , 2007, Clinical Cancer Research.

[33]  E. Glatstein,et al.  Progression-free Survival in Gastrointestinal Stromal Tumours With High-dose Imatinib: Randomised Trial , 2006 .

[34]  J. Blay,et al.  Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. , 2005, European journal of cancer.

[35]  J. Manola,et al.  Cytoreductive Surgery in Patients with Metastatic Gastrointestinal Stromal Tumor Treated with Sunitinib Malate , 2010, Annals of Surgical Oncology.

[36]  A. D. Van den Abbeele,et al.  Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  A. D. Van den Abbeele,et al.  Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. , 2002, The New England journal of medicine.

[38]  J. Desai,et al.  Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  J. Blay,et al.  Outcome of Patients with Platelet-Derived Growth Factor Receptor Alpha–Mutated Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era , 2012, Clinical Cancer Research.

[40]  R. Casadio,et al.  Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST , 2013, European Journal of Human Genetics.

[41]  M. O'sullivan,et al.  SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors , 2013, Modern Pathology.

[42]  J. Blay,et al.  A Phase I Study of Single-Agent Nilotinib or in Combination with Imatinib in Patients with Imatinib-Resistant Gastrointestinal Stromal Tumors , 2009, Clinical Cancer Research.

[43]  Yoon-Koo Kang,et al.  Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group , 2012, Investigational New Drugs.

[44]  M. Heinrich,et al.  Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild‐type gastrointestinal stromal tumours: a comprehensive genotype–phenotype correlation study , 2012, Histopathology.

[45]  C. Antonescu,et al.  Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  H. Harputluoglu,et al.  Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third- or fourth-line treatment: A retrospective multicenter experience , 2013, Oncology letters.

[47]  J. Blay,et al.  KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. , 2006, European journal of cancer.

[48]  H. Joensuu,et al.  Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis. , 2013, European journal of cancer.