A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST).

Trent, Jonathan C.; Wathen, K.; Mehren, Margaret von; Samuels, Brian L.; Staddon, Arthur P.; Choy, Edwin; Butrynski, James E.; Chugh, Rashmi; Chow, Warren; Rushing, Daniel A.; Forscher, Charles; Baker, Laurence H.; Schuetze, Scott M.

doi:10.1200/jco.2011.29.15_suppl.10006

Cited by 61 publications

(40 citation statements)

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“…All of sunitinib-related toxicities can managed with dose interruptions or reductions [68,69,72,73] . Second-generation TKIs like sorafenib, nilotinib, dasatinib and regorafenib have shown activity in patients resistant to imatinib and sunitinib [75][76][77][78][79][80][81][82][83][84][85][86][87][88] . Results with regorafenib are most encouraging.…”

Section: Sunitinib Malatementioning

confidence: 99%

A gist of gastrointestinal stromal tumors: A review

Rammohan¹,

Sathyanesan²,

Rajendran³

et al. 2012

WJGO

156

193

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enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors. AbstractGastrointestinal stromal tumors (GISTs)

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Section: Sunitinib Malatementioning

confidence: 99%

A gist of gastrointestinal stromal tumors: A review

Rammohan¹,

Sathyanesan²,

Rajendran³

et al. 2012

WJGO

156

193

View full text Add to dashboard Cite

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“…1), a total of 51 studies were evaluated for quality. Nineteen studies were considered to be of sufficient quality for inclusion in analyses (5)(6)(7)(8)(9)(10)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Most studies were phase II or III clinical trials, though three retrospective and one prospective observational study were included (25,29,32,36).…”

Section: Resultsmentioning

confidence: 99%

“…Another targeted therapy, regorafenib, is used in patients with GIST with resistance to both imatinib and sunitinib (7). Several new therapies are also being evaluated for later lines of treatment, including the TKIs nilotinib and imatinib in combination with the mTOR inhibitor everolimus (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis for the Association between Overall Survival and Progression-Free Survival in Gastrointestinal Stromal Tumor

Ozer-Stillman¹,

Strand²,

Chang³

et al. 2014

Clin Cancer Res

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Purpose: Gastrointestinal stromal tumor (GIST) is a relatively rare tumor that is treated with targeted therapies in advanced stages. Randomized clinical trials (RCT) often require long followup and large sample sizes to evaluate overall survival (OS), the gold-standard measure of treatment efficacy. However, changes in therapy following disease progression may complicate survival assessments. Establishing surrogate endpoints may facilitate the drug approval and availability of new efficacious treatments; however, no published studies have investigated this topic in unresectable and/or metastatic GIST.Experimental Design: A systematic literature review identified 14 RCTs and five observational studies of sufficient methodologic quality published between January 1995 and December 2013 (29 treatment arms; 2,189 patients). Weighted linear regression was used to evaluate the relation between median OS and median progression-free survival (PFS) for all arms combined and stratified by treatment line, treatment type, and quality score.Results: Median OS and PFS were positively related with a correlation of 0.91. The association was still moderate (correlation 0.72) after eliminating four influential data points. In stratified analyses, correlation of OS and PFS was greater in later lines of therapy (first line ¼ 0.52; second line ¼ 0.80; third-and laterline ¼ 0.70) and imatinib showed a stronger association (0.91) than other evaluated treatments (À0.26 to 0.69).Conclusion: This analysis identified a strong relationship between median OS and PFS, especially in later lines of therapy. Findings suggest that PFS could serve as a surrogate marker for OS; however, analyses of patient-level data are needed to establish its validity in GIST.

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“…Some of these treatments include the previously mentioned HER2 targeted agent pertuzumab, which when combined with trastuzumab and docetaxel in the first-line HER2 positive mBC cancer setting, was not a cost-effective strategy when compared to trastuzumab and docetaxel alone (74). However, a criticism of this analysis was that it failed to account for the sequential (as opposed to one time) drug prescribing practice that is commonly employed in patients with metastatic disease (75). Another emerging treatment option is immune checkpoint inhibitor, pembrolizumab, which acts through the inhibition of programmed death 1 (PD1) and was recently shown in a phase II trial to have an impressive overall response rate in several solid tumors.…”

Section: Future Approvalsmentioning

confidence: 99%