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Metastatic breast cancer: AstraZeneca’s Faslodex (fulvestrant) approved for new indication in the USA

AstraZeneca has announced that the US Food and Drug Administration (FDA) has approved a new indication in the US, expanding the use of Faslodex® (fulvestrant) to include use in combination with Ibrance® (palbociclib). The combination use is for the treatment of women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer (MBC) whose cancer has progressed following endocrine therapy.1 Fulvestrant has been approved in the US since 2002 and in Europe since 2004 as a monotherapy for the treatment of postmenopausal women with HR+ MBC whose cancer has progressed following antioestrogen therapy.

The oestrogen hormone receptor positive (ER+) form of breast cancer is the most common subtype, and is one of the key drivers of disease progression. Preclinical studies show that fulvestrant directly targets the oestrogen receptor (ER) by blocking and degrading the ER, helping to inhibit tumour growth.1,2

“The new Faslodex indication provides another important treatment option for patients, as described in the study, who progressed on or early after prior endocrine therapy. The data supporting combination therapy with Faslodex plus palbociclib showed a clear increase in progression-free survival in patients in the combination arm, as compared to Faslodex and placebo,” said Dr. Dennis Slamon, Professor of Medicine, Chief of the Division of Haematology/Oncology and Executive Vice Chair for Research for UCLA’s Department of Medicine. The FDA approval of this new indication in the US for fulvestrant is based on data from the Phase III PALOMA-3 trial, which met the study’s primary endpoint of progression-free survival (PFS). The combination of fulvestrant 500 mg and palbociclib 125 mg resulted in a 4.9 month PFS improvement over fulvestrant and placebo, in women with HR+ HER2- advanced or MBC whose disease had progressed after endocrine therapy.Improvement in PFS was seen irrespective of menopausal status.1

“This new indication in the US is encouraging news for metastatic breast cancer patients,” said Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca. “As a company we are committed to optimising the current standard of care in breast cancer. To achieve this, we are exploring combinations across different scientific platforms through ongoing research and evaluation.”

The most common adverse reactions (>10%) of any grade reported in PALOMA-3 of fulvestrant plus palbociclib vs fulvestrant plus placebo included neutropenia (83% vs 4%), ?leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs ?28%), anaemia (30% vs 13%), stomatitis (28% vs 13%), headache (26% vs 20%), diarrhoea ?(24% vs 19%), thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and ?pyrexia (13% vs 5%).1

About PALOMA-3

PALOMA-3 is a Phase III international, randomised, double-blind, parallel group, multicentre study of fulvestrant plus palbociclib versus fulvestrant plus placebo conducted in women with HR+/HER2- advanced or metastatic breast cancer, regardless of their menopausal status, whose disease progressed after endocrine therapy. The study evaluated 521 pre/postmenopausal women who were randomised 2:1 to fulvestrant plus palbociclib or fulvestrant plus placebo. Of the study population, 20.7% were either premenopausal (meaning they had not reached menopause), or perimenopausal (meaning that their bodies were making the natural transition toward menopause), and were therapeutically induced to become postmenopausal.1

Patients enroled in this study had a median age of 57 years (range 29 to 88). The majority of patients in the study were white (74%). All patients had an ECOG (Eastern Cooperative Oncology Group) PS of 0 or 1, and 80% were postmenopausal. All patients had received prior systemic therapy and 75% of patients had received a previous chemotherapy regimen. Twenty-five percent of patients had received no prior therapy in the metastatic disease setting, 60% had visceral metastases, and 23% had bone only disease.1

Fulvestrant 500 mg was given as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly (28 ± 3 days) thereafter. Palbociclib was given orally at a dose of 125 mg daily for 21 consecutive days followed by 7 days off treatment. Patients continued to receive their assigned treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. Premenopausal or perimenopausal patients received goserelin for the duration of study treatment, starting at least 4 weeks before randomization and continuing every 28 days.1

About Metastatic Breast Cancer (MBC)

MBC is the most advanced stage of breast cancer (stage four), and occurs when cancer cells have spread beyond the initial tumour 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.3

About Fulvestrant

Fulvestrant is indicated in the European Union (EU) 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.4

Fulvestrant represents a hormonal therapy approach that targets the ER. The ER is a key driver of disease progression. Fulvestrant helps to slow tumour growth by blocking and degrading the ER.1,2 ??