Fulvestrant Superior to Anastrozole as Initial Therapy in Advanced Breast Cancer

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Fulvestrant (Faslodex) was superior to anastrozole as initial treatment of hormone receptor–positive, endocrine therapy–naive, advanced breast cancer, significantly reducing the risk of disease progression or death, according to the results of the phase III FALCON study presented at the 2016 European Society for Medical Oncology (ESMO) Congress.1

These data are fairly consistent with the FIRST phase II study and confirm that fulvestrant is superior to anastrozole.
— Matthew Ellis, MB, BCh, PhD

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“FALCON met the primary endpoint, showing a statistically significant improvement in progression-free survival with fulvestrant as front-line treatment. Quality of life was maintained in patients taking fulvestrant. These data are consistent with the FIRST phase II study and confirm that fulvestrant is superior to anastrozole,” stated Matthew Ellis, MB, BCh, PhD, of Baylor College of Medicine in Houston.

First-line treatment of hormone receptor–positive breast cancer includes endocrine therapy with either tamoxifen or third-generation aromatase inhibitors. In recent years, there has been a shift toward aromatase inhibitors, Dr. Ellis said. Fulvestrant is a selective estrogen receptor degrader currently approved by the U.S. Food and Drug Administration as second-line therapy post disease progression after aromatase inhibitors or tamoxifen. FALCON is a registration trial for front-line therapy.

The phase II FIRST trial had striking results, showing that fulvestrant significantly improved time to disease progression to 23.1 months vs 13.1 months with anastrozole (P = .01), reducing the risk of disease progression by 33%.2 Further, fulvestrant had a survival advantage in the FIRST trial. Median overall survival in the phase II trial was 54.1 months vs 48.1 months with anastrozole (P = .04).

Study Details

The objective of the FALCON trial was to confirm that progression-free survival was superior with fulvestrant compared with anastrozole in postmenopausal women with locally advanced or metastatic hormone receptor–positive, HER2-negative, endocrine-therapy naive breast cancer. Patients were randomized to receive intramuscular fulvestrant at 500 mg on days 0, 1, and 28, then every 28 days vs anastrozole at 1 mg/d; they were treated until disease progression or unacceptable toxicity. Patients were stratified for previous chemotherapy yes or no, measurable vs unmeasurable disease, and locally advanced vs metastatic disease.

At baseline, 75% of patients were white, 34% had a single line of prior chemotherapy (adjuvant therapy or for advanced disease), and all patients had a good performance status. About 55% had visceral metastasis, with slightly more patients in the fulvestrant arm.

Study Results

Median progression-free survival was 16.6 months with fulvestrant vs 13.8 months with anastrozole (P = .0488). Over time, the curves continued to separate, with fulvestrant providing modestly better disease control, Dr. Ellis said.

Fulvestrant vs Anastrozole in Advanced Breast Cancer

  • The phase III FALCON trial confirms the superiority of fulvestrant vs anastrozole for initial treatment of postmenopausal women with advanced hormone receptor–positive breast cancer.
  • Fulvestrant prolonged progression-free survival by an absolute value of 3 months in the overall study population and by almost 10 months in patients with nonvisceral disease.
  • Fulvestrant is an option for single-agent endocrine therapy in low-risk patients.

Subgroup analysis showed that fulvestrant was markedly better than anastrozole in patients with nonvisceral disease: median progression-free survival was 22.3 months vs 13.8 months with anastrozole. Both drugs achieved similar progression-free survival in those with visceral metastases. “This suggests that first-line fulvestrant could be particularly considered in patients with nonvisceral disease,” Dr. Ellis emphasized.

At the time of analysis of these first results, after 25 months of follow-up, there was no difference in overall ­survival.

Median time to deterioration of quality of life did not differ significantly in the two treatment arms: 13.8 months for fulvestrant vs 11.1 months for anastrozole. “There were no safety surprises,” Dr. Ellis indicated. Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation were low and similar between treatment arms.

“Ideally, we need biomarkers that identify patients who are good candidates for fulvestrant monotherapy as their most appropriate first-line option,” he concluded. ■

Disclosure: The FALCON trial was supported by AstraZeneca. Dr. Ellis owns stock in Bioclassifier LLC and has consulted for AstraZeneca, Pfizer, Novartis, and Celgene.


1. 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. 2016 ESMO Congress. Abstract LBA14_PR. Presented October 8, 2016.

2. Ellis MJ, Llombart-Cussac A, Felti D, et al: Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: Overall survival analysis from the phase II FIRST study. J Clin Oncol 33:3781-3787, 2015.

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I think the jury is out on the decision to give combination therapy or single-agent therapy first line. Oncologists have to come to their own conclusions by assessing whether patients are low, intermediate, or high risk.
— Peter Schmid, MD, PhD

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