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

Session Type and Session Title: 
Oral Abstract Session, Sarcoma
Abstract Number: 


J Clin Oncol 29: 2011 (suppl; abstr 10006)
J. C. Trent, K. Wathen, M. von Mehren, B. L. Samuels, A. P. Staddon, E. Choy, J. E. Butrynski, R. Chugh, W. A. Chow, D. A. Rushing, C. A. Forscher, L. H. Baker, S. Schuetze, Sarcoma Alliance for Research through Collaboration; University of Texas M. D. Anderson Cancer Center, Houston, TX; Fox Chase Cancer Center, Philadelphia, PA; Kootenai Cancer Center, Post Falls, ID; University of Pennsylvania, Philadelphia, PA; Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; City of Hope, Duarte, CA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA

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Abstract Disclosures


Background: Dasatinib is an oral tyrosine kinase inhibitor of KIT, PDGFR, ABL and SRC with a distinct binding affinity for KIT and PDGFR. We performed a phase II trial to assess antitumor activity of dasatinib in patients (pts) with advanced GIST who were refractory to imatinib (IM) and sunitinib malate (SM). Methods: Pts received dasatinib 70mg PO BID. Computer tomographic response rates (ORR) was evaluated every 8 wks by Choi criteria. The primary endpoint was a target progression-free survival at 6 months (PFS-6) of >30% with <10% deemed inactive by a Bayesian approach. Objective response rate (ORR) per Choi criteria was also determined. Results: From 8/2008 to 7/2010, 50 pts were accrued (47 evaluable for response). Median age was 60(range, 20-78), 62% were male, and median ECOG PS=1. The most common site of primary disease was stomach (59%) and metastasis was liver (56%). Primary median tumor size at diagnosis was 8.7 cm(range 3.7-26) and mitotic rate was >5/50 hpf in 74% of patients. Tumor morphology was spindled (63%), epithelioid (18%) or mixed (18%). The median number of prior therapies was 2[range 1-6, IM (100%), SM (80%)]. Genotype was available for 15 pts: 6(40%) KIT exon 11, 6(40%) WT, 2(13%) KIT exon 9, and 1(7%) had PDGFR D842V. The median number of cycles was 2 (range, 1-24). The PR rate was 32% (15/47) by Choi criteria. 21% patients (10/47) were progression-free >6 months. Median PFS and OS were 2.0 months and 19 months. Median PFS for patients with WT GIST was 8.4 months (range 1.2-27). Toxicity was assessed in all pts: 14 grade 3 events (28%; constitutional, GI, respiratory, and myelosuppression) and 1 grade 4 event (2%, pain). There were no deaths related to dasatinib. Conclusions: Dasatinib has significant activity by ORR in IM and SM-refractory GIST but did not meet the predefined 6 month PFS rate of 30%. Mutational and molecular correlates are forthcoming.