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Antiestrogen Therapy Is Active in Selected Ovarian Cancer Cases: The Use of Letrozole in Estrogen Receptor–Positive Patients

Authors' Affiliations: ¹ Cancer Research UK Centre, University of Edinburgh, Crewe Road South, Edinburgh, Scotland, United Kingdom, and ² Department of Oncology, Cancer Research UK, Beatson Oncology Centre, Glasgow, United Kingdom

Requests for reprints: John F. Smyth, Cancer Research UK Centre, University of Edinburgh, Crewe Road South, Edinburgh, Scotland, United Kingdom. Phone: 44-1317773512; Fax: 44-1317773520; E-mail: john.smyth{at}ed.ac.uk.

Purpose: To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)–positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease.

Experimental Design: This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor.

Results: Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, ² for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment.

Conclusions: This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.

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