Clinical Review Abstract
Trials in Progress Abstract
Abstracts selected for publication but not presentation at the Annual Meeting
Abstracts granted an exception in accordance with ASCO's Conflict of Interest Policy
A phase II study of dasatanib (BMS 354825) in recurrent or metastatic ckit-expressing adenoid cystic (ACC) and non-ACC malignant salivary glands tumors (MSGT).
Head and Neck Cancer
Head and Neck Cancer
2013 ASCO Annual Meeting
J Clin Oncol 31, 2013 (suppl; abstr 6022)
Author(s): Stuart J. Wong, Ezra E.W. Cohen, Theodore Karrison, David N. Hayes, Merrill S. Kies, Kevin J. Cullen, Tawee Tanvetyanon, Athanassios Argiris, Naoko Takebe, Dean Lim, Nabil F. Saba, Francis P. Worden, Jill Gilbert, Heinz-Josef Lenz, Albiruni R.A. Razak, John D. Roberts, Everett E. Vokes; Medical College of Wisconsin, Milwaukee, WI; The University of Chicago Medicine and Biological Sciences, Chicago, IL; The University of Chicago Medical Center, Chicago, IL; Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Maryland, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; University of Texas Health Science Center at San Antonio, San Antonio, TX; Investigational Drug Branch, Cancer Therapy Evaluation Program, Rockville, MD; City of Hope, Duarte, CA; Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Vanderbilt University, Nashville, TN; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Princess Margaret Hospital, Toronto, ON, Canada; Massey Cancer Center, Richmond, VA
Background: ACC is a rare disease, accounting for 1/3rd of MSGT, in which 90% of cases express the protein product of the ckit proto-oncogene. Dasatinib is a potent and selective inhibitor of five oncogenic PTKs/kinase families including ckit. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. Methods: In a two-stage design, adult patients (pts) with recent radiographic progressive, recurrent or metastatic ACC, + cKIT, were treated with dasatinib 70 mg PO BID. Pts with non-ACC MSGT of other histologic types, were treated as a separate cohort. Response was assessed every 8 wks by imaging using RECIST criteria. The study design stipulated enrollment of n=40 ACC patients (20 in stage I and 20 in stage II) and 25 non-ACC patients (14 in stage I and 11 in stage II). Results: Fifty-four pts were enrolled, 40 ACC and 14 non-ACC. One additional pt was a screen failure. Baseline data on 54 pts are: M:F = 28:26, median age 56.6 yrs (range 20-82), PS 0:1:2 = 24:28:2, prior radiation:chemotherapy = 44:21. The most frequent adverse events experienced (as % of pts, worst grade 2 or higher and at least possibly related to study drug) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (11%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), and non-cardiac chest pain (6%). No grade 4 adverse events occurred and only 15 pts experienced a grade 3 adverse event (at least possibly attributed to study drug), primarily dyspnea (4 patients) and fatigue (3 patients). Significant cardiac toxicity was observed in one pt (grade 3 prolonged QT corrected interval). Among ACC pts, best response to dasatinib: 0 pts (0%) had PR, 21 pts (52%) had SD (range 2.8-13.8 months), 12 pts (30%) had PD, and 2 died prior to cycle 2. Median PFS was 4.8 mos. For 14 evaluable non-ACC pts, none had an objective response, triggering early stopping. 7 had SD (range 1.4-6.6 months), and 4 PD. Conclusions: Although there were no objective responses, dasatinib is well tolerated, with tumor stabilization achieved by 52% of ACC pts. Dasatinib demonstrated no activity in non-ACC MSGT. Clinical trial information: NCT00859937.
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