Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial

  title={Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial},
  author={George D. Demetri and Allan T. van Oosterom and Christopher R. Garrett and Martin E. Blackstein and Manisha H Shah and Jaap Verweij and Grant A. McArthur and Ian Judson and Michael C. Heinrich and Jeffrey A. Morgan and Jayesh Desai and Christopher Fletcher and Suzanne George and Carlo L. Bello and Xin Huang and Charles M. Baum and Paolo Giovanni Casali},
  journal={The Lancet},

Clinical efficacy and safety of sunitinib after imatinib failure in Japanese patients with gastrointestinal stromal tumor.

It is demonstrated that sunitinib may be an effective agent for advanced gastrointestinal stromal tumor after failure of imatinib in clinical practice.

Clinical outcomes of imatinib dose escalation versus sunitinib in first-line imatinib-failure gastrointestinal stromal tumour

Both imatinib dose escalation and sunitinib were optional in Asian patients after failure of first-lineImatinib-failure Asian GIST patients, and patients with KIT exon 11 mutation benefited more from a direct shift to sunit inib.

Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate

The pharmacokinetics observed and clinical outcomes achieved in Japanese GIST patients on sunitinib (50 mg/day, Schedule 4/2) after imatinib failure appeared similar to those of Western patients in previous sunit inib trials.

Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial

Ripretinib was not superior to sunitinib in terms of PFS, however, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripret inib.



Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.

Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, indicating that inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinalStromal tumors, which resist conventional chemotherapy.

Interruption of imatinib (IM) in GIST patients with advanced disease: Updated results of the prospective French Sarcoma Group randomized phase III trial on survival and quality of life

Primary endpoint was progression-free survival (PFS); secondary endpoints were OS, quality of life (QoL), secondary response after IM re-introduction, identification of molecular determinants of response.

Acquired Resistance to Imatinib in Gastrointestinal Stromal Tumor Occurs Through Secondary Gene Mutation

That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or preventImatinib resistance and to employ newer targeted therapies.

Sunitinib (SU) response in imatinib-resistant (IM-R) GIST correlates with KIT and PDGFRA mutation status.

  • M. HeinrichR. Maki G. Demetri
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2006
The findings suggest that, similar to prior results observed using imatinib, CB of SU following failure of IM treatment is significantly influenced by both primary and secondary mutations in the predominant pathogenic kinase, the uncontrolled activity of which is a critical etiologic factor for GIST.

Bevacizumab: An Angiogenesis Inhibitor with Efficacy in Colorectal and Other Malignancies

Although clinical knowledge on the effectiveness of bevacizumab is limited, early data indicate that it is a promising agent, with a novel mechanism of action, for patients with metastatic cancer, including colorectal cancer.

Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants.

This study shows the high frequency of KIT/PDGFRA kinase domain mutations in patients with secondary resistance and defines genomic amplification of Kit / PDGFRA as an alternative cause of resistance to the drug.

Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor.

  • M. HeinrichC. Corless J. Fletcher
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2003
Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib.