AstraZeneca, a global, innovation-driven biopharmaceutical business, announced that the US Food and Drug Administration (FDA) has approved a new indication expanding the use of Faslodex (fulvestrant) to include use in combination with 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 after endocrine therapy.

Faslodex has been approved since 2002 as a monotherapy for the treatment of postmenopausal women with HR+ MBC whose cancer has progressed following antiestrogen therapy.

Estrogen receptor (ER) positive breast cancer is the most common subtype of breast cancer and one of the key drivers of disease progression for this subtype is through the ER. Laboratory studies show that Faslodex directly targets the ER by blocking and degrading the ER, helping to inhibit tumor growth.

“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 Hematology/Oncology and executive vice chair for research for UCLA's Department of Medicine.

The FDA approval of this new indication for Faslodex 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 Faslodex 500 mg and palbociclib 125 mg resulted in a 4.9 month PFS improvement over Faslodex 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.

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

“We believe that advances in cancer treatment will come, in part, from our research building upon existing treatments. This new indication adds to the existing body of evidence supporting Faslodex -based therapy for certain metastatic breast cancer patients in an area where there is still a high unmet medical need,” said Andrew Coop, vice president, US Medical Affairs, Oncology at AstraZeneca.

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

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

Faslodex 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.

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.

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.

Faslodex is approved for the treatment of postmenopausal women with HR+ MBC with disease progression following antiestrogen therapy. Faslodex  is also indicated for use in combination with palbociclib for the treatment of women with HR+, HER2- advanced or MBC whose disease progressed after endocrine therapy.1

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