High-Dose Fulvestrant for Advanced Breast Cancer

Summary and Comment |
January 28, 2014

High-Dose Fulvestrant for Advanced Breast Cancer

  1. William J. Gradishar, MD

A modest improvement in survival without an increase in toxicity is confirmed.

  1. William J. Gradishar, MD

The prior phase III, randomized CONFIRM trial compared the previously approved dose of fulvestrant (250 mg every 28 days) versus a higher dose (500 mg every 28 days plus an additional 500 mg on day 14 of the first month) in postmenopausal women with locally advanced or metastatic estrogen-receptor–positive breast cancer that recurred or progressed after endocrine therapy (NEJM Journal Watch Oncol Hematol Nov 9 2010). The initial analysis showed that higher-dose fulvestrant significantly improved progression-free survival (PFS) without increasing toxicity. Based on those results, 500 mg is now the approved dose of fulvestrant in the U.S., Japan, and Europe.

Now, the CONFIRM investigators have completed a final analysis of survival that was prospectively planned to be conducted after 75% of patients had died. In the trial, 736 postmenopausal women (median age, 61) were randomized to 250 mg or 500 mg of fulvestrant.

At the final analysis, 554 (75.3%) of the patients had died. Median overall survival was longer with 500 mg versus 250 mg of fulvestrant (26.4 vs. 22.3 months; hazard ratio, 0.81; P=0.02).


These results confirm that the higher dose and schedule of fulvestrant translates into longer survival for patients. The magnitude of improvement was arguably modest, but it was achieved with no increase in adverse effects. Ultimately, extending the benefit of endocrine therapy further will likely be achieved by combining this approach with agents directed at signaling pathways that influence the development of resistance.

Editor Disclosures at Time of Publication

  • Disclosures for William J. Gradishar, MD at time of publication Consultant / Advisory board Biologics, Inc.; Celgene; Myriad; Novartis Grant / research support Breast Cancer Research Fund Editorial boards Clinical Breast Cancer; Journal of Clinical Oncology; Oncology


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