• Breast Cancer
• Menopause
• Hormone Therapy
• Oncology Clinical Trials

The Comparison of Fulvestrant 250 mg and 500 mg in Postmenopausal Women with Oestrogen Receptor Positive Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy [CONFIRM] trial compared treatment with 2 doses of fulvestrant (250 vs 500 mg) in postmenopausal women with locally advanced or metastatic estrogen receptor (ER)-positive breast cancer that had recurred or progressed after endocrine therapy. The primary analysis showed that progression-free survival (PFS) was significantly increased with fulvestrant 500 versus 250 mg [Di Leo A et al. J Clin Oncol 2010]. The final analysis of OS was presented by Angelo Di Leo, MD, Hospital of Prato, Prato, Italy.

In the CONFIRM trial, eligible patients were randomized to fulvestrant 250 mg (1 injection) plus placebo (1 injection; n=374) versus fulvestrant 500 mg (2 injections; n=362) on Days 0, 14, and 28, and every 28 days thereafter. The primary endpoint was PFS [Di Leo A et al. J Clin Oncol 2010]. The final analysis of OS was planned and conducted after 75% of the patients had died. After the primary analysis, patients receiving fulvestrant 250 mg were allowed to switch to 500 mg. The median age in both groups was 61 years and all patients were ER-positive. Eight (2.1%) of 374 patients in the fulvestrant 250-mg group switched to fulvestrant 500 mg.

At the first analysis, median PFS was 6.5 months with fulvestrant 500 mg versus 5.5 months with the 250-mg dose (HR, 0.80; 95% CI, 0.68 to 0.94; p=0.006). The first analysis of OS at 50% maturity showed that the median time to death was 25.1 months with fulvestrant 500 mg versus 22.8 months with fulvestrant 250 mg (HR, 0.84; 95% CI, 0.69 to 1.03; p=0.091) [Di Leo A et al. J Clin Oncol 2010].

The final analysis of OS at 75% maturity (full analysis set) demonstrated a median time to death of 26.4 months with fulvestrant 500 mg versus 22.3 months with 250 mg (HR, 0.81; 95% CI, 0.69 to 0.96; nominal p=0.016 [cannot be claimed as statistically significant]).

Serious adverse events (SAEs) were reported in 9.7% of patients taking fulvestrant 500 mg and 7.2% of those taking fulvestrant 250 mg. Treatment-related SAEs were reported in 2.2% of patients receiving 500 mg versus 1.1% receiving 250 mg. SAEs resulting in death during the whole treatment period occurred in 1.5% receiving 500 mg versus 2.0% receiving 250 mg.

Consistent with the previously reported PFS and OS data, the final OS analysis at 75% maturity showed that fulvestrant 500 mg is associated with a 4.1-month increase in median OS and a 19% reduction in the risk of death compared with fulvestrant 250 mg. Analysis of the first subsequent therapies does not support an imbalance between the 2 study arms. Only 2% of patients crossed over from 250 to 500 mg. However, activity for 500 mg after pretreatment with 250 mg is unknown. The safety results do not support a clinically relevant difference between fulvestrant 250 and 500 mg, and are consistent with the previously reported safety profile of fulvestrant 500 mg.

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