Exemestane and Chemotherapy as First-line Treatment of Metastatic Breast Cancer: Results of a Phase II Study

Abstract Background Metastatic breast cancer remains largely incurable. Strategies involving the combination of the selective estrogen receptor modulator tamoxifen and chemotherapy have been abandoned in view of unacceptable toxicity because of thromboembolic events. The aim of this study was to investigate the safety and efficacy of the third-generation steroidal aromatase inhibitor exemestane plus chemotherapy. Patients and Methods Postmenopausal women with advanced breast cancer received 6 cycles of intravenous chemotherapy (5-fluorouracil [5-FU], epirubicin, and cyclophosphamide) and exemestane 25 mg/day that was continued after chemotherapy was completed. The primary efficacy endpoint was time to progression (TTP), and response rates were also assessed. Safety was assessed from adverse events. Results Twenty-three patients (median age, 62 years) were included in this study. Twenty patients completed 6 chemotherapy cycles. Median TTP was 13.7 months. Overall response was achieved by 20 patients (73.9%), and the clinical benefit rate was 87%. During the chemotherapy plus exemestane treatments, 50 adverse events were reported in 14 of the 23 patients (60.9%). As expected, the incidence of adverse events decreased during the phase of exemestane treatment alone (19 adverse events in 10 of 20 patients [50%]). There were 2 grade 4 events reported, pulmonary embolism and pneumonia, although pneumonia was not considered to be related. Conclusion Although a small number of patients were included, the combination of exemestane and chemotherapy was well tolerated and only 1 thromboembolic event was reported. Response rates were similar to other comparable series and may encourage further studies to confirm the efficacy of chemotherapy in combination with an aromatase inhibitor.