The Lynx Group

Benefit of Higher Doses of Fulvestrant Confirmed

March 2013, Highlights

Although many clinicians are already prescribing fulvestrant (Faslodex) at a dose of 500 mg, a phase 3 study presented at the meeting confirmed the superiority of this dose over 250 mg.

Three years ago, the first results of the randomized, multicenter, phase 3 CONFIRM trial showed a significantly better progression-free survival (PFS) with 500 mg in women with estrogen receptor (ER)-positive metastatic breast cancer. The final analysis shows an overall survival (OS) advantage as well, although in the unadjusted analysis, the difference did not achieve statistical significance, reported Angelo Di Leo, MD, PhD, Head of Sandro Pitigliani Medical Oncol­-ogy Unit, Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, in Italy.

“These results are consistent with the previously reported PFS and OS data,” Dr Di Leo said. “Based on the results of the present trial, whenever fulvestrant is considered for the treatment of menopausal patients with ER-positive advanced breast cancer, the recommended dose is 500 mg.”

Women are typically considered for fulvestrant after they have failed treatment with tamoxifen (Nolvadex) and aromatase inhibitors.

Although fulvestrant has been available for more than 10 years, clinicians have not widely embraced it. Some specialists contend that the drug was suboptimally dosed at 250 mg, the US Food and Drug Administration–approved dose, and speculate that outcomes might be more robust if higher doses were used, which the analysis of the CONFIRM trial sought to determine. The analysis was conducted when 75% of the patients had died.

The study involved 736 women with ER-positive metastatic breast cancer who had progressed or recurred after treatment with another antiestrogen drug. Patients were randomized to 1 of the 2 doses of fulvestrant and followed until disease progression or until death.

At the final analysis, a 1-month improvement in the median PFS was observed with the higher-dose group (6.5 months vs 5.5 months, respectively; P = .006), and the median OS improved from 22.3 months to 26.4 months, which was a 19% reduction in risk (P = .016).

Dr Di Leo said that the P value came from an unadjusted exploratory analysis that lacked the statistical power to reflect true differences between the arms; however, he emphasized that a clear trend toward improved survival has emerged between the earlier analysis and the final analysis.

“It is interesting to highlight the concept that the 2 survival analyses are perfectly consistent,” he said. “They are leading to the same conclusion, and that conclusion is that there is an increased benefit in terms of survival for patients who receive 500 mg of fulvestrant.”

During treatment and follow-up, 35 patients in the 500-mg fulvestrant arm had at least 1 serious adverse event compared with 27 patients who received 250 mg. A serious adverse event leading to death occurred in 5 patients in the 500-mg fulvestrant arm compared with 6 patients in the 250-mg fulvestrant arm.

These safety results do not support any clinically relevant difference between 250 mg and 500 mg of fulvestrant, and “they are consistent with the previously reported safety profile of fulvestrant 500 mg,” Dr Di Leo said.

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