Originally published as JCO Early Release 10.1200/JCO.2007.15.8808 on June 30 2008

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Phase II Study of Erlotinib in Recurrent or Metastatic Endometrial Cancer: NCIC IND-148

Amit M. Oza, Elizabeth A. Eisenhauer, Laurie Elit, Jean-Claude Cutz, Akira Sakurada, Ming S. Tsao, Paul J. Hoskins, Jim Biagi, Prafull Ghatage, John Mazurka, Diane Provencher, Naomi Dore, Janet Dancey, Anthony Fyles

From the Princess Margaret Hospital, University Health Network, University of Toronto, Toronto; National Cancer Institute of Canada Clinical Trials Group, Queen's University; Cancer Centre of Southeastern Ontario, Kingston; Juravinski Cancer Centre, Hamilton, Ontario; BC Cancer Agency Vancouver Clinic, Vancouver, British Columbia; Tom Baker Cancer Centre, Calgary, Alberta; Centre Hospitalier de L'Université de Montréal, Montreal, Quebec, Canada; and the Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda MD

Corresponding author: Amit M. Oza, MD (Lon), FRCP, FRCPC, Princess Margaret Hospital, University Health Network, Bras Family Drug Development Program, 610 University Avenue, Suite 5-700, Toronto, Ontario, M5G 2M9, Canada; e-mail: amit.oza{at}uhn.on.ca

Purpose Epidermal growth factor receptor (EGFR) overexpression is common in endometrial cancers and may have a major role in tumor growth and progression. Erlotinib is an orally active, selective inhibitor of EGFR tyrosine kinase activity.

Patients and Methods A multinomial design two-stage phase II study was performed to evaluate single-agent activity of erlotinib in women with advanced endometrial cancer with recurrent or metastatic disease who were chemotherapy naïve and had received up to one line of prior hormonal therapy. Erlotinib was administered at daily dose of 150 mg. Archival tumor tissue was analyzed for EGFR expression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). Mutational status of EGFR was determined in responders.

Results Thirty-two of 34 entered patients are assessable for response. Treatment was well tolerated and severe toxicity infrequent, with the only grade 4 toxicity being an elevation of transaminases (AST). There were four confirmed partial responses (PRs; 12.5%; 95% CI, 3.5% to 29%) lasting 2 to 36 months. Fifteen patients had stable disease (SD), with median duration of 3.7 months (range, 2 to 12 months). EGFR expression was analyzed in thirty patients; 19 were positive, nine were negative, and two were not assessable. Of the 19 patients who were EGFR positive, three had PR (16%), seven SD, and eight progressive disease, and one was not assessable. No mutations were identified in responders. FISH showed no correlation of response with gene amplification.

Conclusion Erlotinib is well tolerated with an overall objective response rate of 12.5%. Molecular analysis did not identify EGFR mutations in responders or correlation of response with gene amplification.

published online ahead of print at www.jco.org on June 30, 2008.

Supported by grants from the National Cancer Institute of Canada with funds received from the Canadian Cancer Society; correlative translational studies were supported by research grants (A.M.O.) and the Bras Drug Development Program.

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

Clinical trial information can be found for the following: NCT00030485 [ClinicalTrials.gov] .

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