Phase Ill Trial Shows Improved Progression-Free Survival With Fulvestrant vs Anastrozo... Page 1 of 6
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`Phase III Trial Shows Improved
`Progression-Free Survival With
`fulvestrant vs Anastrozole in
`,Advanced Breast Cancer
`
`3 B
`
`y Matthew Stenger
`
`March 10, 2017
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`In the international phase III FALCON trial, reported in The Lancet, Iohn
`F.R. Robertson, MD, of the University of Nottingham, United Kingdom,
`and colleagues found that progression—free survival was improved with
`intramuscular fulvestrant (Faslodex) vs oral anastrozole in endocrine
`
`therapy—naive womenwith hormone receptor (HR)—positive locally
`
`advanced or metastatic breast cancer.1
`
`Study Details
`
`In the double—blind trial, 462 patients from 113 sites in 20 countries in Asia, Europe, North
`
`America, South America, and South Africa were randomly assigned between October 2012 and
`
`July 2014 to receive fulvestrant (n : 230) or anastrozole (n : 232). Fulvestrant was given as
`
`500—mg intramuscular injections on days 0, 14, 28, and every 28 days thereafter; anastrozole
`
`was given at 1 mg orally daily. The primary endpoint was progression-free survival in the
`
`intent—to—treat population.
`
`For the fulvestrant and anastrozole groups, median age was 64 and 62 years (47% and 39% 2
`
`65 years); 76% and 75% were white, and 16% and 15% were Asian; time from diagnosis was 2
`
`1 year for 30% and 29%; 76% and 77% were estrogen receptor— and progesterone receptor
`
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`Phase Ill Trial Shows Improved Progression-Free Survival With Fulvestrant vs Anastrozo... Page 2 of 6
`
`“ Fulvestrant has superior
`efficacy and is a preferred
`
`treatment option for patients
`
`with hormone receptor
`
`—positive locally advanced or
`metastatic breast cancer
`
`—positive; 88% and 86% had metastatic disease;
`
`59% and 51% had Visceral disease; 84% and 84%
`
`had measureable disease;16% and 19% had received
`
`chemotherapy for locally advanced or metastatic
`
`disease; and 23% and 22% had received
`
`radiotherapy.
`
`who have not received
`
`Progression—Free Survival
`
`previous endocrine therapy
`
`compared with a third-
`
`generation aromatase
`
`inhibitor, a standard of care
`
`for first-line treatment of
`
`these patients.
`
`— John F. R. Robertson,
`
`MD, and colleagues
`
`Median progression—free survival was 16.6 months
`
`(95% confidence interval [CI] : 13.83—20.99
`
`months) in the fulvestrant group vs 13.8 months
`
`(95% CI : 11.99—16.59 months) in the anastrozole
`
`group (hazard ratio [HR] : 0.797, (95% CI : 11.99
`
`—16.59 months) in the anastrozole group (hazard
`
`ratio [HR] : 0.797, 95% CI : o.637—o.999, P
`
`: .0486). Among patients with measurable disease,
`
`an objective response was observed in 46% (89/193)
`
`of fulvestrant recipients and 45% (88 /196) of
`
`anastrozole recipients (odds ratio : 1.07, 95% CI : 0.72—1.61, P : .7290); the median duration
`
`of response was 20.0 (95% CI : 15.90—27.63) vs 13.2 (95% CI : 10.64—16.72) months.
`
`Hormone Therapy in Advanced
`Breast Cancer
`
`The magnitude of progression—free survival
`benefit with fulvestrant was consistent across
`
`most prespecified subgroups, except for patients
`
`- Fulvestrant improved progression-free
`
`with previous chemotherapy for locally advanced
`
`survival vs anastrozole among patients
`
`or metastatic disease, patients with
`
`with no prior endocrine therapy.
`- The benefit of fulvestrant vs
`
`anastrozole was more marked in
`
`patients with nonvisceral disease.
`
`nonmeasurable disease, patients who were not
`
`estrogen receptor— and progesterone receptor
`
`—positive, and patients with Visceral disease. For
`
`example, hazard ratios were 0.59 (95% CI : 0.42
`
`—0.84; median progression—free survival : 22.3
`
`[95% CI : 16.62—32.79] vs 13.8 months [95% CI : 11.04—16.59]) among patients with
`
`nonvisceral disease and 0.99 (95% CI : 0.74—1.33; median progression—free survival : 13.8
`
`[95% CI : 11.04—16.53] vs 15.9 [95% CI : 11.27—16.89]) among those with visceral disease
`
`(post hoc interaction test P : .0092).
`
`Median overall survival could not yet be calculated. At data cutoff, death had occurred in 29%
`
`of the fulvestrant group vs 32% of the anastrozole group (HR : 0.88, 95% CI : 0.63—1.22, P
`
`=.4277)
`
`Adverse Events
`
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`Phase Ill Trial Shows Improved Progression-Free Survival With Fulvestrant vs Anastrozo... Page 3 of 6
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`The most common adverse events of any grade were arthralgia (17% in fulvestrant group vs
`
`10% in anastrozole group) and hot flushes (11% vs 10%). Grade 2 3 adverse events occurred in
`
`22% vs 18%. Serious adverse events occurred in 13% vs 13%. Adverse events of special
`
`interest—ie, joint disorders and back pain—occurred in 26% vs 18%. Adverse events led to
`
`discontinuation of treatment in 7% vs 5%. A total of 3% of patients in each group died, but
`
`none of the deaths were considered to be related to study treatment.
`
`The authors concluded: “Fulvestrant has superior efficacy and is a 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, a standard of care for first—line treatment of these patients.” I
`
`Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors,
`visit www.thelancet.com.
`
`Reference
`
`1. Robertson IF, Bondarenko 1M, Trishkina E, et a1: Fulvestrant 500 mg versus anastrozole 1
`
`mg for hormone receptor—positive advanced breast cancer (FALCON 1: An international,
`
`randomised, double—blind, phase 3 trial. Lancet 388:2991—3005, 2016.
`
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