WILMINGTON, Del.--(EON: Enhanced Online News)--AstraZeneca today announced results from a pre-specified subgroup analysis of the positive Phase III FALCON trial suggesting that treatment effects in terms of progression-free survival (PFS) were largely consistent across the subgroups analyzed with some possible exceptions, including patients with non-visceral disease. The FALCON trial assessed FASLODEX® (fulvestrant) 500 mg compared to ARIMIDEX® (anastrozole) 1 mg in the 1st line endocrine treatment of postmenopausal women who were initially diagnosed with locally-advanced or metastatic breast cancer who had not had prior hormonal treatment for hormone receptor positive (HR+) breast cancer.1
The results, presented during a poster session at the 2016 San Antonio Breast Cancer Symposium (SABCS), showed a decreased risk of progression by 41% (Hazard ratio: 0.592; 95% confidence interval (CI): 0.419-0.837), in women whose disease has not spread to organs within the chest or abdomen (defined as non-visceral disease), when compared with ARIMIDEX.1,2 In this subgroup, median PFS was 22.3 months for FASLODEX vs 13.8 months for ARIMIDEX. In patients with visceral disease, the treatment effect for FASLODEX vs ARIMIDEX was comparable (Hazard ratio: 0.993; 95% CI: 0.740-1.331).1
Serious adverse events (SAEs) in the non-visceral disease subgroup occurred in 11.6% of patients with FASLODEX versus 16.8% of patients with ARIMIDEX. In the visceral disease subgroup, SAEs occurred in 14.3% of patients with FASLODEX vs 10.1% of patients with ARIMIDEX.1
Aromatase inhibitors, such as ARIMIDEX, are the current standard of care in 1st line treatment for postmenopausal women with HR+ advanced breast cancer. 3,4,5
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The findings from this subgroup analysis build upon the existing body of clinical evidence for FASLODEX. AstraZeneca is committed to investigating the potential of FASLODEX in the 1st line setting for women with advanced breast cancer alongside the development of new targeted medicines and immunotherapies for women with all types of early and advanced breast cancer.”
John Robertson, MD, Professor of Surgery, University of Nottingham, Royal Derby Hospital Centre, United Kingdom noted: “This subgroup analysis has identified a cohort of patients with non-visceral disease who may derive even longer disease control from fulvestrant over anastrozole when compared to patients with visceral disease. Data from the FIRST trial, a head-to-head Phase II trial that showed both improved disease control and a survival benefit in favor of fulvestrant corroborate the findings reported in the visceral and non-visceral subgroups in FALCON. Together, these findings indicate that fulvestrant may offer an important treatment option in advanced breast cancer for this population of patients.”
The FALCON trial met its primary endpoint and revealed a median PFS of 16.6 months in the FASLODEX arm compared to 13.8 months median PFS in the ARIMIDEX arm (Hazard ratio 0.797; 95% CI: 0.637-0.999; p=0.0486). The FALCON data was recently published online in The Lancet and was presented at the 2016 European Society for Medical Oncology meeting.6
The safety and tolerability profile was in line with current experience with FASLODEX and ARIMIDEX. The most commonly reported AEs in the FASLODEX and ARIMIDEX arms were arthralgia (17% vs 10%), hot flashes (11% vs 10%), and nausea (11% vs 10%), respectively.1,6
AstraZeneca is pursuing a label extension with US regulatory authorities to include the FALCON results in the FASLODEX label.
FASLODEX is currently approved as a monotherapy in the US for the treatment of HR+ metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.7
ARIMIDEX is currently approved in the US for the first-line treatment of postmenopausal women with HR+ or hormone receptor unknown locally advanced or metastatic breast cancer. ARIMIDEX is also approved for the treatment advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.5
Important Safety Information About FASLODEX
- FASLODEX is contraindicated in patients with known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with FASLODEX
Risk of Bleeding
- Because FASLODEX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or in patients on anticoagulants
- FASLODEX is metabolized primarily in the liver. A 250-mg dose is recommended in patients with moderate hepatic impairment (Child-Pugh class B). FASLODEX has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C)
Injection Site Reaction
- Use caution while administering FASLODEX at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with FASLODEX injection
Embryo-Fetal Toxicity and Lactation
- Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during FASLODEX treatment and for 1 year after the last dose. Advise lactating women not to breast-feed during treatment with FASLODEX and for one year after the final dose because of the potential risk to the infant
Immunoassay Measurement of Serum Estradiol
- Due to structural similarity of FASLODEX and estradiol, FASLODEX can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels
Adverse Reactions Monotherapy
- The most common adverse reactions occurring in ≥5% of patients receiving 500 mg FASLODEX were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation
- Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX users and were not dose-dependent
- The most frequently reported serious adverse reactions in patients receiving FASLODEX plus palbociclib were infections (3%), pyrexia (1%), neutropenia (1%) and pulmonary embolism (1%)
- The most common adverse reactions (≥10%) of any grade reported in patients receiving FASLODEX plus palbociclib were: neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia
Indications for FASLODEX Monotherapy
- FASLODEX is indicated for the treatment of hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy
- FASLODEX in combination with palbociclib is indicated for the treatment of HR- positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy
Please see full Prescribing Information with Patient Information.
Important Safety Information About ARIMIDEX
- Prescription ARIMIDEX is only for postmenopausal women. ARIMIDEX should not be taken if you are pregnant because it may harm your unborn child. Do not take ARIMIDEX if you are allergic to any of its ingredients
- Based on information from a study in patients with early breast cancer, women with a history of blockages in heart arteries (ischemic heart disease) who take ARIMIDEX may have a slight increase in this type of heart disease compared to similar patients who take tamoxifen
- ARIMIDEX can cause bone softening/weakening (osteoporosis) increasing the chance of fractures. In a clinical study in early breast cancer, there were more fractures (including fractures of the spine, hip, and wrist) with ARIMIDEX (10%) than with tamoxifen (7%)
- In a clinical study in early breast cancer, some patients taking ARIMIDEX had an increase in cholesterol. Skin reactions, allergic reactions, and changes in blood tests of liver function have also been reported
- In the early breast cancer clinical trial, the most common side effects seen with ARIMIDEX include hot flashes, joint symptoms (including arthritis and arthralgia), weakness, mood changes, pain, back pain, sore throat, nausea and vomiting, rash, depression, high blood pressure, osteoporosis, fractures, swelling of arms/legs, insomnia, and headache
- In advanced breast cancer trials, the most common side effects seen with ARIMIDEX versus tamoxifen include hot flashes, nausea, decreased energy and weakness, pain, back pain, headache, bone pain, increased cough, shortness of breath, sore throat, and swelling of arms and legs. Joint pain/stiffness has been reported in association with the use of ARIMIDEX
- ARIMIDEX should not be taken with tamoxifen or estrogen-containing therapies
Approved Uses for ARIMIDEX
ARIMIDEX is approved for adjuvant treatment (treatment following surgery with or without radiation) of postmenopausal women with hormone receptor-positive early breast cancer.
ARIMIDEX is approved for the initial treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of postmenopausal women with advanced breast cancer that has progressed following treatment with tamoxifen. Patients with hormone receptor-negative disease and patients who did not previously respond to tamoxifen therapy rarely responded to ARIMIDEX.
For more information, see your doctor.
Please see full Prescribing Information.
NOTES TO EDITORS
The FALCON (Fulvestrant and AnastrozoLe COmpared in hormonal therapy Naive advanced breast cancer) study is a Phase III, randomized, double-blind, multicenter trial. The study compared the efficacy and tolerability profile of a 500 mg dose of FASLODEX plus placebo with a 1 mg dose of ARIMIDEX plus placebo, in postmenopausal women with hormone receptor-positive, locally advanced or metastatic breast cancer, who have not had prior hormonal therapy.8,9
The FALCON trial was designed, based on positive results from the Phase II FIRST trial, which demonstrated a greater median overall survival (nearly six months) with FASLODEX, when compared to ARIMIDEX.9
About Advanced Breast Cancer or Metastatic Breast Cancer (ABC/MBC) Advanced/metastatic breast cancer refers to Stages III and IV breast cancer. Stage III disease may be referred to as locally advanced breast cancer. MBC is the most advanced stage of breast cancer (stage IV), and occurs when cancer cells have spread beyond the initial tumor site to other parts of the body outside of the breast. Since there is no cure for metastatic breast cancer, the goal of current treatment is to delay disease progression.10,11,12
It is estimated that in 2016, there will be approximately 151,000 women in the US living with MBC, and this number is projected to increase to approximately 160,000 by the year 2020.13
About FASLODEX (fulvestrant)
FASLODEX is approved for the treatment of postmenopausal women with HR+ MBC whose cancer has progressed following antiestrogen therapy. On March 2, 2016, the US Food and Drug Administration (FDA) approved FASLODEX, in combination with palbociclib, for the treatment of US women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+, HER2-) advanced or metastatic breast cancer (MBC), whose cancer has progressed after endocrine therapy.7,14
FASLODEX represents a hormonal therapy approach that targets the estrogen receptor (ER). The ER is a key driver of disease progression. FASLODEX helps to slow tumor growth by blocking and degrading the ER.7,15
About ARIMIDEX (anastrozole)
ARIMIDEX is approved for adjuvant treatment (treatment following surgery with or without radiation) of postmenopausal women with hormone receptor-positive early breast cancer. ARIMIDEX is approved for the initial treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of postmenopausal women with advanced breast cancer that has progressed following treatment with tamoxifen. Patients with hormone receptor-negative disease and patients who did not previously respond to tamoxifen therapy rarely responded to ARIMIDEX.5
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – immuno-oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
- Robertson J, Noguchi S, Shao Z, et al. Progression-Free Survival Results In Patient Subgroups From A Phase 3 Randomized Trial Of Fulvestrant 500 Mg Vs Anastrozole For Hormone Receptor-Positive Advanced Breast Cancer (FALCON). Presented at the San Antonio Breast Cancer Symposium (SABCS), 6-10 December 2016. San Antonio, Texas.
- National Cancer Institute, NCI Dictionary of Cancer Terms – Visceral. Available Online. Accessed December 2016.
- Rugo H. The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. Ann Oncol. 2007;10.1093:1-12. Accessed December 2016.
- National Cancer Institute. Breast Cancer Treatment (PDQ®) Healthcare Professionals version. Available Online. Last Updated February 2, 2016. Accessed December 2016.
- ARIMIDEX (anastrozole) Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
- Robertson JFR, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung K-L, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Results from the Phase III, randomised, double-blind, Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): a randomised, double-blind, Phase 3 trial. Lancet 2016. Accessed December 2016.
- FASLODEX Full Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
- A Global Study to Compare the Effects of Fulvestrant and Anastrozole in a Subset of Patients With Breast Cancer. (FALCON) ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Available Online NLM Identifier: NCT01602380 Accessed December 2016.
- Ellis MJ, Llombart-Cussac A, Feltl 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. 2015 Nov 10;33(32):3781-7. Accessed December 2016.
- Cleveland Clinic. Diseases and Conditions: Breast Cancer. Available Online. Last Updated September 5, 2013. Accessed December 2016.
- Mayo Clinic. Breast Cancer Diagnosis. Available Online. Last Updated August 16, 2016. Accessed December 2016.
- American Cancer Society. What Is Advanced Cancer? Atlanta: American Cancer Society; 2014. Available online. Accessed December 2016.
- CancerMPact.Khapps.com: ONC-Prevalence of Metastatic Breast Cancer in Women 2014-2020. Accessed December 2016.
- FDA Approval Letter. U.S. Food and Drug Administration, Silver Spring, MD.
- Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44.