Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors

Stuart J. Wong, T. Karrison, D. N. Hayes, M. S. Kies, K. J. Cullen, T. Tanvetyanon, A. Argiris, N. Takebe, D. Lim, N. F. Saba, F. P. Worden, J. Gilbert, H. J. Lenz, A. R.A. Razak, J. D. Roberts, E. E. Vokes, E. E.W. Cohen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. Patients and methods: In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i.d. Responsewas assessed every 8 weeks using RECIST. Results: Of 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28: 26, median age 56 years (range 20-82 years), ECOG performance status 0: 1: 2 = 24: 28: 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as%of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progressionfree survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2. Conclusion: Although there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50%of ACC patients. Dasatinib demonstrated no activity in non-ACCMSGT.

Original languageEnglish (US)
Article numbermdv537
Pages (from-to)318-323
Number of pages6
JournalAnnals of Oncology
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2016

    Fingerprint

Keywords

  • Adenoid cystic carcinoma
  • Dasatinib
  • Malignant salivary gland cancer
  • Phase II
  • cKIT

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Wong, S. J., Karrison, T., Hayes, D. N., Kies, M. S., Cullen, K. J., Tanvetyanon, T., Argiris, A., Takebe, N., Lim, D., Saba, N. F., Worden, F. P., Gilbert, J., Lenz, H. J., Razak, A. R. A., Roberts, J. D., Vokes, E. E., & Cohen, E. E. W. (2016). Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors. Annals of Oncology, 27(2), 318-323. [mdv537]. https://doi.org/10.1093/annonc/mdv537