High-dose fulvestrant benefits advanced breast cancer patients
MedWire News: Patients taking high-dose fulvestrant for advanced breast cancer experience a longer period without disease progression than patients taking lower-dose fulvestrant, study findings indicate.
Importantly, the increased dose was not accompanied by increased toxicity, indicating a "clinically meaningful improvement in benefit versus risk" compared with the lower dose, say the researchers.
At the time of the study, the US Food and Drug Administration (FDA) approved dose for fulvestrant was 250 mg every 28 days, and there were suggestions that a higher dose might be associated with increased clinical and biologic activity.
To see if this was indeed true, Angelo Di Leo (Hospital of Prato, Italy) and colleagues set up the phase III Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) trial, in which fulvestrant 250 mg every 28 days was compared with a higher dose regimen that incorporated a day 14 loading element: 500 mg on days 0, 14, and 28, and every 28 days thereafter.
In total, 735 postmenopausal women with estrogen receptor-positive, advanced, or metastatic breast cancer who had experienced progression after prior endocrine therapy were enrolled in the study, and randomly assigned to one of the two treatment groups.
The researchers report a significantly longer median progression-free survival among patients in the high-dose group (n=362), at 6.5 months, compared with those in the lower dose group (n=374), at 5.5 months. The corresponding reduction in risk for progression was 20%.
At 12 months, 34% and 25% of patients remained progression-free on fulvestrant 500 and 250 mg, respectively. At 24 months, these figures were 16% and 11%, respectively.
Furthermore, duration of clinical benefit was significantly prolonged in the high-dose group (16.6 vs 13.9 months) and there was a trend toward longer overall survival in the high-dose group compared with the lower-dose group (25.1 vs 22.8 months).
In contrast, the clinical benefit rate was not significantly better for the high-dose group at 45.6% versus 39.6% in the lower-dose group.
Safety analyses revealed that fulvestrant 500 mg was well tolerated with no dose-dependent adverse events.
"These results indicate that fulvestrant 500 mg, given on a monthly basis after the loading schedule, should replace the currently approved 250 mg schedule in current medical practice," Di Leo and co-authors conclude in the Journal of Clinical Oncology.
Of note, since the publication of the study, the FDA has approved the 500 mg dose of fulvestrant for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy.
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By Laura Dean