Palbociclib Receives FDA Approval and Expanded Indication for First-Line Metastatic Breast Cancer

On March 31, the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for a first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor, palbociclib (Ibrance), based on the results from the confirmatory phase III trial PALOMA-2. The FDA action converts the accelerated approval of palbociclib to regular approval and broadens the range of antihormonal therapy that may be administered with palbociclib. Palbociclib now is indicated in combination with an aromatase inhibitor, expanding on its earlier indication in combination with letrozole, as initial endocrine-based therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

Palbociclib is the first CDK4/6 inhibitor approved by the FDA. Palbociclib was granted accelerated approval in combination with letrozole in February 2015 and regular approval in February 2016 for a second indication: the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy. Today, palbociclib plus letrozole is the most prescribed FDA-approved oral combination treatment for HR-positive, HER2-negative metastatic breast cancer.

“In the 2 years since its initial approval, palbociclib has been prescribed to more than 50,000 patients by more than 9,800 physicians in the United States,” said Liz Barrett, Global President and General Manager, Pfizer Oncology. “This important update to the palbociclib label underscores the strength of the data we continue to generate for palbociclib. We are proud of the impact this innovative medicine continues to have on patients’ lives.”


The updated label is based on data including results from the phase III PALOMA-2 trial, which evaluated palbociclib as first-line therapy in combination with letrozole for postmenopausal women with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer. These data were published by Finn et al in The New England Journal of Medicine.

PALOMA-2 demonstrated that the combination of palbociclib and letrozole significantly extended progression-free survival compared with letrozole plus placebo. The median progression-free survival of the palbociclib-and-letrozole combination exceeded 2 years, making it the first treatment for this population of women to do so in a phase III study. The median progression-free survival for women treated with palbociclib plus letrozole exceeded the median progression-free survival for placebo plus letrozole by more than 10 months (24.8 months [95% confidence interval [CI] = 22.1–not estimable] vs 14.5 months [95% CI = 12.9–17.1]) for women treated with letrozole plus placebo (hazard ratio = 0.58, 95% CI = 0.46–0.72; < .0001), and represented a 42% reduction in the risk of disease progression.

The warnings and precautions of palbociclib include neutropenia and embryofetal toxicity. Adverse reactions in PALOMA-2 were generally consistent with the known adverse reaction profile for palbociclib and no major unexpected safety findings were observed. The most common grade 3/4 adverse reactions with palbociclib plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%). Febrile neutropenia was reported in 2.5% of patients in the palbociclib plus letrozole group and none of the patients in the placebo plus letrozole group.

The full prescribing information for palbociclib can be found here.

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®.