Faslodex (Fulvestrant) Significantly Improves Overall Survival For Women With Hormone Receptor Positive Breast Cancer Compared To Arimidex<sup>�</sup> (Anastrozole)
The latest findings presented today at the 2014 San Antonio Breast Cancer Symposium (SABCS) show that investigational first-line treatment with fulvestrant resulted in a significant improvement in overall survival (OS) of 5.7 months, compared with anastrozole in postmenopausal patients with hormone receptor positive (HR+) locally advanced or metastatic breast cancer.1
These latest OS (a secondary endpoint) results from the Phase II randomised, open-label FIRST (Fulvestrant fIRst-line Study comparing endocrine Treatments) study at a median follow-up of 48.8 months, show an increase in median OS of 5.7 months for fulvestrant compared to anastrozole (54.1 months vs. 48.4 months respectively) and a 30% reduction in the risk of death (HR 0.70; 95% CI 0.50, 0.98; p=0.041). Furthermore, this OS treatment effect was generally consistent irrespective of patient age, progesterone-receptor status, presence of visceral disease or prior hormone or chemotherapy (pre-defined sub-groups).1
The safety and tolerability profile remained consistent with previous findings, with both treatment arms being well tolerated (serious adverse events; 23.8% for fulvestrant versus 21.4% for anastrozole).1 The most common adverse events (AEs) in the fulvestrant group following the primary analysis were bone pain (13.9%), nausea (10.9%), arthralgia (9.9%), constipation (9.9%), vomiting (8.9%), and dyspnea (8.9%).2
“Postmenopausal patients with advanced stages of hormone receptor positive breast cancer continue to face an unmet need. An extension in overall survival of almost six months in the FIRST study represents a clinically meaningful benefit for this patient group,” said Professor John Robertson, lead investigator and Professor of Surgery at the University of Nottingham, UK.
These updated findings from the FIRST study provide evidence supporting the important role fulvestrant can potentially play in the future of treatment of postmenopausal women with advanced HR+ breast cancer. Previous data from the primary analysis of this study demonstrated that fulvestrant was as effective in terms of clinical benefit rate (CBR) as anastrozole2 while significantly delaying time to progression (TTP; 23.4 months vs. 13.1 months; HR 0.66; 95% CI 0.47, 0.92; p=0.010);3 no new safety concerns for fulvestrant were documented.
“These new findings are encouraging and we look forward to the results of the ongoing Phase III FALCON study, which is investigating the use of fulvestrant compared to anastrozole in hormone therapy naïve, advanced breast cancer patients,” said Antoine Yver, Head Oncology, Global Medicines Development at AstraZeneca. “Fulvestrant is just one example of how, for more than 40 years, we have been developing drugs that have significantly increased treatment options for cancer patients around the world. It is a legacy we are building on within our portfolio, which we believe has the potential to redefine the treatment paradigm for cancer.”
About fulvestrant (FASLODEX 500mg)
The main goals of metastatic breast cancer treatment are to delay disease progression and extend survival.4 FASLODEX is approved for the treatment of postmenopausal women with oestrogen receptor positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on therapy with an anti-oestrogen.5 FASLODEX represents a hormonal therapy approach that targets the oestrogen receptor. FASLODEX blocks and degrades oestrogen receptors, leading to downregulation. Consequently, oestrogen receptor signalling leading to tumour growth is disrupted.5,6,7,8
About the FIRST study1,3
The FIRST (Fulvestrant fIRst-line Study comparing endocrine Treatments) study is a Phase II, randomised, open-label study that compared the use of fulvestrant (delivered by intramuscular injection on days 0, 14, 28 and every 28 days thereafter) with anastrozole 1mg (taken orally once daily). Patients had not received any prior endocrine therapy for advanced disease. The primary endpoint was clinical benefit rate (CBR), defined as the proportion of patients experiencing an objective response or stable disease for ≥24 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), duration of response, and duration of clinical benefit. The study included 205 patients from 62 centres across nine countries.
The most common AEs in the fulvestrant group following the primary analysis were bone pain (13.9%), nausea (10.9%), arthralgia (9.9%), constipation (9.9%), vomiting (8.9%), and dyspnoea (8.9%).2
Important safety information about FASLODEX® (fulvestrant) injection
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.
Because FASLODEX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or in patients on anticoagulants.
FASLODEX is metabolised primarily in the liver. A 250mg dose is recommended in patients with moderate hepatic impairment. FASLODEX has not been evaluated in patients with severe hepatic impairment (Child-Pugh Class C).
Foetal harm can occur when administered to a pregnant woman. Women should be advised of the potential hazard to the foetus and to avoid becoming pregnant while receiving FASLODEX.
?The most common, clinically significant adverse reactions occurring in ≥5% of patients receiving FASLODEX were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flush, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnoea, and constipation.
Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX users and were non dose-dependent.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
CONTACTS
Media Enquiries
Esra Erkal-Paler +44 20 7604 8030 (UK/Global)
Vanessa Rhodes +44 20 7604 8037 (UK/Global)
Ayesha Bharmal +44 20 7604 8034 (UK/Global)
Jacob Lund +46 8 553 260 20 (Sweden)
Michele Meixell + 1 302 885 6351 (US)
Investor Enquiries
Thomas Kudsk Larsen +44 20 7604 8199 mob: +44 7818 524185
Karl Hård +44 20 7604 8123 mob: +44 7789 654364
Anthony Brown +44 20 7604 8067 mob: +44 7585 404943
Eugenia Litz +44 20 7604 8233 mob: +44 7884 735627
Christer Gruvris +44 20 7604 8126 mob: +44 7827 836825
References
- Robertson JF, et al. Fulvestrant 500 mg versus anastrozole as first-line treatment for advanced breast cancer: overall survival from the Phase II ‘FIRST’ study. Presented at the San Antonio Breast Cancer Symposium (SABCS), San Antonio, Texas; 9-13 December 2014.
- Robertson JF, et al. Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. J Clin Oncol. 2009 Sep 20;27(27):4530-5.
- Robertson JF, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized 'FIRST' study. Breast Cancer Res Treat. 2012 Nov;136(2):503-11
- National Cancer Institute. Metastatic Cancer: Questions and Answers. Available online. Last accessed October 2014.
- European Medicines Agency. Faslodex Summary of Product Characteristics. Available online: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000540/WC500021174.pdf Last accessed: 8th December 2014.
- Howell A. Is fulvestrant (“Faslodex”) just another selective estrogen receptor modulator? Int J Gynecol Cancer.2006;16(2):521-523.
- Carlson RW. The history and mechanism of action of fulvestrant. Clin Breast Cancer. 2005;6(suppl 1):S5-S8.
- Wakeling AE. Similarities and distinctions in the mode of action of different classes of antioestrogens. Endocr Relat Cancer. 2000;7(1):17-28.
Learning Zones
The Learning Zones are an educational resource for healthcare professionals that provide medical information on the epidemiology, pathophysiology and burden of disease, as well as diagnostic techniques and treatment regimens.
1 mins