FALCON Breast Cancer Trial: Who's Naive Here?

Lidia Schapira, MD


January 06, 2017

Fulvestrant 500 mg Versus Anastrozole 1 mg for Hormone Receptor-Positive Advanced Breast Cancer (FALCON): An International, Randomized, Double-Blind, Phase 3 Trial

Robertson JFR, Bondarenko I, Trishkina E, et al
Lancet. 2016;388:2997-3005

Study Summary

Aromatase inhibitors are a standard of care for hormone receptor–positive locally advanced or metastatic breast cancer. FALCON is the first randomized, double-blind, multicenter trial to assess the efficacy and safety of monotherapy with the estrogen downregulator fulvestrant compared with aromatase inhibitors for a population of women with advanced breast cancer who had not received prior endocrine therapy.

A total of 524 eligible patients were randomly assigned to receive fulvestrant (500 mg intramuscular injection; on days 0, 14, 28, then every 28 days thereafter) or anastrozole. The primary endpoint was progression-free survival.

The study found that progression-free survival was significantly longer in the fulvestrant group than in the anastrozole group (hazard ratio [HR], 0.797). Median progression-free survival was 16.6 months (95%) in the fulvestrant group versus 13.8 months in the anastrozole group.

The hardest question to answer is whether to use monotherapy or combination therapy.

The most common adverse events were arthralgia (38 [17%] in the fulvestrant group versus 24 [10%] in the anastrozole group) and hot flashes (26 [11%] in the fulvestrant group versus 24 [10%] in the anastrozole group). A small percentage of patients—16 (7%) of 228 patients in the fulvestrant group and 11 (5%) of 232 patients in the anastrozole group—discontinued treatment because of adverse events. Patients with nonvisceral metastases derived the greatest benefit from fulvestrant.

The investigators concluded thatfulvestrant was superior to anastrozole and is the preferred treatment option for patients with hormone receptor–positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy compared with a third-generation aromatase inhibitor, which is the standard of care for first-line treatment of these patients.


Clinicians are still challenged when it comes time to pick the initial endocrine therapy for postmenopausal patients with advanced or metastatic breast cancer that is hormone receptor positive. We have several good options, and the hardest question to answer is whether to use monotherapy or combination therapy. Most patients develop a recurrence after being exposed to adjuvant endocrine therapy, which in most cases consists of monotherapy with an aromatase inhibitor or a sequential regimen of tamoxifen followed by an aromatase inhibitor. This study, while informative, compared different agents in a population that was treatment naive.

It is noteworthy that patients who had disease confined to bone (and whose tumors were strongly estrogen receptor positive) did better on fulvestrant. We now need to identify molecular diagnostics to help guide treatment recommendations, so that we can provide patients with personalized plans for treatment on the basis of expectations of clinical benefit and expected toxicities from such treatments.



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