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A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.