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

On February 19, 2016, the U.S. Food and Drug Administration approved palbociclib (Ibrance) in combination with fulvestrant for the treatment of women with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer with disease progression following endocrine therapy. 

In February 2015, the FDA granted accelerated approval for palbociclib in combination with letrozole for the treatment of hormone receptor–positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women.

Today’s approval is based on the demonstration of an improvement in progression-free survival in an international, randomized, double-blind, parallel group, multicenter study comparing palbociclib plus fulvestrant to placebo plus fulvestrant. Women enrolled had hormone receptor–positive, HER2-negative advanced or metastatic breast cancer with disease progression on or after prior adjuvant or metastatic endocrine therapy. 

Study Details

A total of 521 pre- and postmenopausal women were randomly assigned (2:1) to either palbociclib plus fulvestrant or placebo plus fulvestrant until disease progression or unacceptable toxicity. Palbociclib was administered orally at a dose of 125 mg daily for 21 consecutive days followed by 7 days off treatment. Fulvestrant was administered intramuscularly at a dose of 500 mg on days 1, 15, and 29, and once monthly thereafter. Pre- or perimenopausal women were enrolled in the study and received the luteinizing hormone–releasing hormone agonist goserelin (Zoladex) for at least 4 weeks prior to palbociclib administration and for the study’s duration.

Among the 521 patients, 80% were postmenopausal, all patients had received prior systemic therapy, and 75% had received a previous chemotherapy regimen. Twenty-five percent had not received prior therapy for metastatic disease, 60% had visceral metastases, and 23% had bone disease only.

The major efficacy outcome measure was investigator-assessed progression-free survival evaluated according to RECIST version 1.1. The study demonstrated an improvement in progression-free survival with a hazard ratio of 0.46 (95% confidence interval [CI] = 0.36–0.59, < .0001). The median progression-free survival was 9.5 months vs 4.6 months for patients treated in the palbociclib-plus-fulvestrant and placebo-plus-fulvestrant arms, respectively. 

Safety data were evaluated in 345 patients who received palbociclib plus fulvestrant. The most common (≥ 10%) grade 1 to 4 adverse reactions were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia. The most common grade 3 to 4 adverse reactions were neutropenia (66%) and leukopenia (31%). 

The most frequently reported serious adverse reactions in patients receiving palbociclib plus fulvestrant were infections, pyrexia, neutropenia, and pulmonary embolism. Dose reductions due to an adverse reaction of any grade occurred in 36% of patients and permanent discontinuation associated with an adverse reaction occurred in 6% of patients. 

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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