The FALCON Study: A Phase 3 Comparison of Fulvestrant and Anastrozole in ER+ Advanced Breast Cancer

Recommended first-line treatments for postmenopausal women with hormone receptor–positive advanced/metastatic breast cancer include third-generation aromatase inhibitors (ie, anastrozole) or tamoxifen. Fulvestrant, is a complete estrogen receptor (ER) antagonist approved for the treatment of ER+ advanced breast cancer after aromatase inhibitors have failed. Although a previous phase 2 study was unable to show a difference in clinical benefit rate (CBR) between first-line fulvestrant and anastrozole in these patients, “the median time to progression was significantly increased in patients receiving fulvestrant, which unusually translated into increased overall survival [OS],” said Dr Matthew Ellis of Houston, TX, an author of the subsequent FALCON study.

The FALCON study was a phase 3, randomized, double-blind, multicenter trial designed to confirm the superiority of fulvestrant over anastrozole in postmenopausal women with ER+ and/or progesterone receptor–positive (PR+) advanced breast cancer who had not received prior endocrine therapy.

Patients were randomized 1:1 to fulvestrant (500 mg intramuscularly on days 0, 14, 28, then every 28 days thereafter) or anastrozole (1 mg daily). The primary end point was progression-free survival (PFS) assessed via Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines, surgery/radiotherapy for worsening of disease, or death. Secondary end points were OS; objective response rate (ORR; defined as the percentage of patients recording partial response or complete response [CR]); duration of response (DoR); expected DoR (EDoR); CBR (defined as the proportion of patients recording RECIST assessments of CR/partial response or stable disease over at least 24 weeks); duration of clinical benefit (DoCB); expected DoCB; health-related quality of life (HRQoL); and safety.

In total, 462 patients were randomized to receive fulvestrant (n = 230) or anastrozole (n = 232). The primary end point was met as shown by statistically significant improvement in PFS with fulvestrant (16.6 months) versus anastrozole (13.8 months) (hazard ratio [HR], 0.797; 95% confidence interval [CI], 0.637-0.999; P = 0.0486). Notably, patients without visceral disease showed a larger response to fulvestrant than those with visceral disease (HR 0.59 vs 0.99, respectively). Survival statistics were immature at the time these data were presented, with 31% maturity of OS at a median follow-up of 25 months. “No real difference was seen in ORR,” said Dr Ellis, although based on the EDoR ratio of fulvestrant to anastrozole (ratio, 1.52; 95% CI, 1.23-1.89; P <0.001), “50% of patients are more likely to stay in response with fulvestrant.”

The impact of treatment on HRQoL was similar in both treatment groups, and no new safety findings were observed. The most common adverse events were arthralgia (16.7% vs 10.3%) and hot flashes (11.4% vs 10.3%) for fulvestrant and anastrozole, respectively.

“Overall, these results confirm the superior efficacy of fulvestrant over anastrozole in postmenopausal women with ER+ and/or PR+ locally advanced or metastatic breast cancer who have not received prior hormone therapy,” concluded Dr Ellis.

Ellis M, et al. ESMO 2016. Abstract LBA14.