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Phase II Study of Lapatinib in Recurrent or Metastatic Epidermal Growth Factor Receptor and/or erbB2 Expressing Adenoid Cystic Carcinoma and Non–Adenoid Cystic Carcinoma Malignant Tumors of the Salivary Glands

Mark Agulnik, Ezra W.E. Cohen, Roger B. Cohen, Eric X. Chen, Everett E. Vokes, Sebastien J. Hotte, Eric Winquist, Scott Laurie, D. Neil Hayes, Janet E. Dancey, Shirley Brown, Gregory R. Pond, Ian Lorimer, Manijeh Daneshmand, James Ho, Ming-Sound Tsao, Lillian L. Siu

From the Princess Margaret Hospital Phase II Consortium, Toronto, Canada; Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL; The University of North Carolina, Chapel Hill, NC; and National Cancer Institute, Bethesda, MD

Address reprint requests to Lillian L. Siu, MD, Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, 610 University Ave, Suite 5-718, Toronto, Ontario, M5G 2M9, Canada; e-mail: lillian.siu{at}uhn.on.ca

Purpose Expression of erbB2 and/or epidermal growth factor receptor (EGFR) is associated with biologic aggressiveness and poor prognosis in malignant salivary gland tumors (MSGTs). This phase II study was conducted to determine the antitumor activity of lapatinib, a dual inhibitor of EGFR and erbB2 tyrosine kinase activity, in MSGTs.

Patients and Methods Patients with progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1+ EGFR and/or 2+ erbB2 were treated with lapatinib 1,500 mg daily, in a two-stage cohort. Patients with non-ACC MSGTs were treated as a separate single-stage cohort.

Results Of 62 patients screened, 29 of 33 (88%) ACC and 28 of 29 (97%) non-ACC patients expressed EGFR and/or erbB2. Forty patients with progressive disease were enrolled onto the study. Among 19 assessable ACC patients, there were no objective responses, 15 patients (79%) had stable disease (SD), nine patients (47%) had SD 6 months, and four patients (21%) had progressive disease (PD). For 17 assessable non-ACC patients, there were no objective responses, eight patients (47%) had SD, four patients (24%) had SD 6 months, and nine patients (53%) had PD. The most frequent adverse events were grade 1 to 2 diarrhea, fatigue, and rash. Eight paired tumor biopsies for correlative studies were procured; results did not correlate with clinical outcome.

Conclusion Although no responses were observed, lapatinib was well tolerated, with prolonged tumor stabilization of 6 months in 36% (95% CI, 21% to 54%) of assessable patients. The antitumor effects of lapatinib in MGSTs appear mainly cytostatic, hence evaluation of other molecular targeted agents, or combinations with lapatinib, may be considered. Continued efforts should be made to gain better understanding into the biology of this heterogeneous group of malignancies.

Supported by National Cancer Institute Contracts No. N01-CM-62203 and N01-CM-57018-16, and Translational Research Initiative Contract No. 22XS108-09.

Presented in part at the 2006 American Society of Clinical Oncology Annual Meeting, June 2-6, 2006, Atlanta, GA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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