FDA Approves Fulvestrant in Combination With Abemaciclib in Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer

Today, the U.S. Food and Drug Administration (FDA) approved a new indication for fulvestrant (Faslodex), expanding the drug's approved use to include combined therapy with abemaciclib (Verzenio), a cyclin-dependent kinase (CDK) 4/6 inhibitor, for the treatment of hormone receptor–positive, HER2-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy. Fulvestrant was also approved today by the European Commission (EC) for use in combination with another CDK4/6 inhibitor—palbociclib (Ibrance)—for hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.

About MONARCH 2

The FDA approval is based on data from the phase III MONARCH 2 trial, which met the study’s primary endpoint of progression-free survival. The trial included 669 women with hormone receptor–positive, HER2-negative advanced breast cancer whose disease progressed on or after neoadjuvant or adjuvant endocrine therapy, within 12 months from the end of adjuvant endocrine therapy, or while receiving first-line endocrine therapy for metastatic disease.  

Participants were randomly assigned to receive intramuscular injection of fulvestrant at 500 mg with abemaciclib or placebo orally twice daily in a 2:1 ratio. Pre/perimenopausal women were enrolled in the study and received the gonadotropin-releasing hormone agonist goserelin acetate (Zoladex) for at least 4 weeks prior to and for the duration of the study. Patients remained on treatment until the development of progressive disease or unmanageable toxicity.

Patients enrolled in this study had a median age of 60 years (range = 32–91). The majority of patients in the study were white (56%). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Approximately 59% of patients in each of the treatment arms—fulvestrant in combination with abemaciclib and fulvestrant with placebo—received endocrine therapy as their first therapy for advanced breast cancer; the remaining 38% of patients in the experimental and control treatment arms received this regimen as their second endocrine therapy for advanced breast cancer. Overall, 55.8% had visceral disease and 26.9% had bone-only disease; 25% of patients had primary endocrine resistance, and 2.7% had locally advanced disease.

The results showed a statistically significant increase in investigator-assessed median progression-free survival of 7.1 months (16.4 vs 9.3 months) in patients who received fulvestrant at 500 mg and abemaciclib at 150 mg over fulvestrant and placebo (hazard ratio [HR] = 0.553, 95% confidence interval [CI] = 0.449­­–0.681; P < .0001).

Detailed results of the MONARCH 2 trial were published by Sledge et al in the Journal of Clinical Oncology.

About PALOMA 3

The EC approval is based on data from the phase III PALOMA-3 trial, an international, randomized, double-blind, parallel group, multicenter study of fulvestrant plus palbociclib vs fulvestrant plus placebo conducted in women with hormone receptor–positive, HER2-negative 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 randomized 2:1 to fulvestrant plus palbociclib or fulvestrant plus placebo. Women who were either premenopausal or perimenopausal were therapeutically induced to become postmenopausal and represented 20.7% of the study population.

Patients enrolled in this study had a median age of 57 years (range = 29–88). The majority of patients in the study were white (74%). All patients had an ECOG performance status 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 22% had bone-only disease.

Fulvestrant at 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.

The trial showed a statistically significant increase in investigator-assessed median progression-free survival of 4.9 months (9.5 vs 4.6 months) in patients who received fulvestrant at 500 mg and palbociclib at 125 mg over fulvestrant and placebo (HR = 0.46, 95% CI = 0.36–0.59; P < .0001).

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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