FDA Approves Frontline Fulvestrant for HR-Positive/HER2-Negative Breast Cancer

Matthew Ellis, MD, PhD

The FDA has approved fulvestrant (Faslodex) for use in hormone receptor (HR)-positive, HER2-negative locally-advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy.

The approval is based on results from the phase III FALCON trial, which showed that fulvestrant extended median progression-free survival (PFS) by 2.8 months compared with the aromatase inhibitor anastrozole (16.6 vs 13.8 months; hazard ratio, 0.797; 95% CI: 0.637-0.999; P = .049).

“This study provides evidence that using fulvestrant as the first option for previously untreated hormone receptor-positive advanced breast cancer will prolong the time before the disease advances and alternative therapies are required,” Matthew Ellis, MD, PhD, director of the Lester and Sue Smith Breast Center, part of the NCI-designated Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, said in a statement.

For postmenopausal women with HR-positive advanced or metastatic breast cancer, the recommended first-line treatment includes endocrine therapy with an aromatase inhibitor or tamoxifen. Fulvestrant is a selective estrogen receptor-degrader approved for treatment of advanced HR-positive breast cancer that has progressed following anti-estrogen therapy.

Pivotal data from FALCON were reported at the 2016 ESMO Congress. A total of 462 treatment-naïve patients were randomly assigned to 500 mg of fulvestrant on days 0, 14, 28 (n = 230) or 1 mg daily of anastrozole (n = 232). Eligible patients had received no prior endocrine therapy, although treatment with 1 prior chemotherapy regimen was permitted. Patients were randomized to fulvestrant or anastrozole and followed until disease progression or discontinuation for adverse events.

Three-fourths of the patients tested positive for both estrogen- and progesterone-receptor expression. About 87% of the patients had metastatic disease, as opposed to locally advanced breast cancer. Rates of visceral metastasis were 58.7% in the fulvestrant arm and 51.3% in the anastrozole arm.

Patients without visceral metastases especially benefited from treatment with fulvestrant. The median PFS in patients without visceral metastases was 22.3 months with fulvestrant versus 13.8 months with anastrozole. Patients with visceral metastases had similar PFS with fulvestrant (13.8 months) or anastrozole (15.9 months).

Overall response rate and clinical benefit rate did not differ significantly between groups. Fulvestrant resulted in a median duration of response of 20.0 months as compared with 13.2 months with anastrozole. Median duration of clinical benefit was 22.1 months with fulvestrant and 19.1 months with anastrozole. Expected duration of response also favored fulvestrant (11.4 vs 7.5 months; P = .001), as did expected duration of clinical benefit (21.9 vs 17.5 months; P = .001).

Rates of adverse events, serious adverse events, and adverse events leading to discontinuation were similar between treatment groups. The most commonly reported adverse events with fulvestrant and anastrozole, respectively, were arthralgia (16.7% vs 10.3%), hot flashes (11.4% vs 10.3%), and nausea (10.5% vs 10.3%).

Fulvestrant has been approved in the United States since 2002 for the treatment of ER-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy.

In February 2016, the FDA approved fulvestrant in combination with palbociclib (Ibrance) for women with HR-positive, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine therapy.

Ellis MJ, Bondarenko I, Trishkina E, et al. FALCON: a phase III randomised trial of fulvestrant 500 mg vs. anastrozole for hormone receptor-positive advanced breast cancer. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA14.