Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable GI Stromal Tumor After Failure of Imatinib and Sunitinib: A Multicenter Phase II Trial

George, Suzanne; Wang, Qian; Heinrich, Michael C.; Corless, Christopher L.; Zhu, Mei‐Jun; Butrynski, James E.; Morgan, Jeffrey A.; Wagner, Andrew J.; Choy, Edwin; Tap, William D.; Yap, Jeffrey T.; Abbeele, Annick D. Van den; Manola, Judith; Solomon, Sarah; Fletcher, Jonathan A.; Mehren, Margaret von; Demetri, George D.

doi:10.1200/jco.2011.39.9394

Cited by 227 publications

(187 citation statements)

References 23 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…However, 16 of 25 of patients had been treated with more than two prior TKIs before study entry. The nine patients in our study who were treated with pazopanib as third-line therapy received a median of two cycles [1][2][3][4][5][6][7][8][9] which is comparable with nilotinib, but inferior to regorafenib [1][2][3]. The fact that our patients were heavily pretreated with multiple TKIs may have affected the outcome of this trial possibly due to multiple secondary mutations.…”

Section: Discussionmentioning

confidence: 99%

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

et al. 2014

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

et al. 2014

View full text Add to dashboard Cite

“…The clinical benefi t rate was 75% due to 4 PRs and 22 instances of SD more than 16 weeks; moreover, the median PFS was 10 months ( 89 ). Preclinical studies have suggested a potential role for FGF pathway activation in the resistance to imatinib ( 60 ).…”

Section: Overcoming Drug Resistancementioning

confidence: 99%

Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives

et al. 2013

View full text Add to dashboard Cite

The fi broblast growth factor/fi broblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifi cations, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, classspecifi c toxicity profi les and correctly designing clinical trials to address these different issues.Signifi cance: FGF/FGFR pathway deregulations are increasingly recognized across different human cancers. Understanding the mechanisms at the basis of these alterations and their multiple roles in cancer promotion and drug resistance is a fundamental step for further implementation of targeted therapies and research strategies. Cancer Discov;3(3);

show abstract

“…In a phase I/II study which had included a total of 97 metastatic, imatinib-resistant GISTs, of which 9 were wild-type GISTs, sunitinib was more active in KIT exon 9 mutant and wild-type GISTs than KIT exon 11 mutations (Heinrich et al 2008). In the group of treatment failures after imatinib and sunitinib, administration of regorafenib showed significant activity, with median PFS of 12 months (George et al 2012). Likewise, pazopanib demonstrated a potential response in heavily pretreated patients, though only five wild-type GIST patients were recruited in this phase II study .…”

Section: Carney-stratakis Syndromementioning

confidence: 99%

Classification of gastrointestinal stromal tumor syndromes

Gopie

Faber

et al. 2018

Endocrine-Related Cancer

View full text Add to dashboard Cite

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, thought to derive from neoplastic outgrowth of the interstitial cells of Cajal. Building on recent advances in recognition, classification and diagnosis, the past two decades have seen a changing paradigm with molecular diagnostics and targeted therapies. KIT and PDGFRA mutations account for 85-90% of GIST carcinogenesis. However, the remaining 10-15% of GISTs, which until recently were called KIT/PDGFRA wild-type GISTs, have been found to have one of the several mutations, including in the SDHA, B, C, D, BRAF and NF1 genes. Though most of such GISTs are sporadic, a number of families with high incidence rates of GISTs and other associated clinical manifestations have been reported and found to harbor germline mutations in KIT, PDGFRA, SDH subunits and NF1. The goal of this review is to describe the mutations, clinical manifestations and therapeutic implications of syndromic and inherited GISTs in light of recent studies of their clinicopathologic range and pathogenesis.

show abstract

Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable GI Stromal Tumor After Failure of Imatinib and Sunitinib: A Multicenter Phase II Trial

Abstract: Regorafenib has significant activity in patients with advanced GIST after failure of both imatinib and sunitinib. A phase III trial of regorafenib versus placebo is ongoing to define more fully the safety and efficacy of regorafenib in this setting.

Cited by 227 publications

References 23 publications

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives

Classification of gastrointestinal stromal tumor syndromes

Contact Info

Product

Resources

About