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CA125 Response Is Associated with Estrogen Receptor Expression in a Phase II Trial of Letrozole in Ovarian Cancer

Identification of an Endocrine-sensitive Subgroup

Imperial Cancer Research Fund Medical Oncology Unit [A. B., H. G., S. P. L., M. S., A. Y., J. F. S.] and Department of Pathology [A. L.], Western General Hospital, Edinburgh EH4 2XU, United Kingdom

Purpose: This study was an open-label Phase II trial of the aromatase inhibitor letrozole (Femara) in patients with relapsed ovarian cancer with evaluation of possible biological markers for response.

Experimental Design: 60 patients were treated with letrozole (2.5 mg daily) at the time of CA125 relapse. Disease response was assessed by Union International Contre Cancer (UICC) criteria and by CA125 measurement. Estrogen receptor (ER), progesterone receptor, epidermal growth factor receptor, erbB2, and HSP27 were measured by immunohistochemistry in paraffin-fixed material obtained from the primary tumors at initial surgery.

Results: 50 patients were evaluable by UICC criteria, and although no complete or partial responses were obtained, 10 patients had stable disease on scan for at least 12 weeks. CA125 responses were evaluable in 54 patients. A partial marker response (>50% decrease) was seen in 5, and the marker remained stable in an additional 14 patients (25% increase). Tumors from the UICC stable disease group had significantly higher ER (P = 0.027) and progesterone receptor (P = 0.0066) values than the progressive disease group, and a combination of these was strongly associated with stable disease (P < 0.0001). Using CA125 criteria, comparison of the CA125 stable/responding disease with progressive disease indicated that tumors with higher ER (P = 0.013), lower erbB2 (P = 0.026), and higher epidermal growth factor receptor (P = 0.009) were associated with CA125 stable/responsive disease.

Conclusions: These results imply that letrozole treatment can produce disease stabilization and CA125 responses that in turn are linked to higher levels of ER expression. These data suggest the presence of an endocrine-sensitive group that could be targeted in future studies.

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