The US Food and Drug Administration (FDA) has approved Pfizer's supplemental New Drug Application (sNDA) for its first-in-class cyclin dependent kinase 4/6 (CDK 4/6) inhibitor, Ibrance (palbociclib), based on the results from the confirmatory phase 3 trial PALOMA-2.
The FDA action converts the accelerated approval of Ibrance to regular approval and broadens the range of anti-hormonal therapy that may be administered with Ibrance. Ibrance 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-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer.
Ibrance is the first CDK 4/6 inhibitor approved by the FDA. Ibrance 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+, HER2- advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy. Today, Ibrance plus letrozole is the most prescribed FDA-approved oral combination treatment for HR+, HER2- metastatic breast cancer.
“In the two years since its initial approval, Ibrance has been prescribed to more than 50,000 patients by more than 9,800 physicians in the US,” said Liz Barrett, global president and general manager, Pfizer Oncology. “This important update to the Ibrance label underscores the strength of the data we continue to generate for Ibrance. 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 3 PALOMA-2 trial, which evaluated Ibrance as first-line therapy in combination with letrozole for postmenopausal women with estrogen receptor-positive (ER+), HER2- metastatic breast cancer. These data were published in the November 17, 2016 issue of The New England Journal of Medicine. PALOMA-2 demonstrated that the combination of Ibrance and letrozole significantly extended progression-free survival (PFS), or the amount of time before tumor growth, compared with letrozole plus placebo. The median PFS of the Ibrance and letrozole combination exceeded two years – making it the first treatment for this population of women to do so in a Phase 3 study. The median PFS for women treated with Ibrance plus letrozole exceeded the median PFS for placebo plus letrozole by more than 10 months (24.8 months [95% CI, 22.1, not estimable] vs. 14.5 months [95% CI, 12.9, 17.1] for women treated with letrozole plus placebo (HR=0.58 [95% CI, 0.46, 0.72], p<0.0001)), and represented a 42% reduction in the risk of disease progression.
The warnings and precautions of Ibrance include neutropenia and embryo-fetal toxicity. Adverse reactions in PALOMA-2 were generally consistent with the known adverse reaction profile for Ibrance and no major unexpected safety findings were observed. The most common grade 3/4 adverse reactions with Ibrance plus letrozole versus 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 Ibrance plus letrozole group and none of the patients in the placebo plus letrozole group.
Palbociclib (Ibrance) is the only treatment for HR+, HER2- metastatic breast cancer with two category 1 recommendations from the National Comprehensive Care Network (NCCN). On March 13, the NCCN updated their recommendation for palbociclib plus letrozole as a first-line treatment for postmenopausal women with HR+, HER2- metastatic breast cancer to a category 1 recommendation. In addition, palbociclib plus fulvestrant is recommended (category 1) for postmenopausal women with HR+, HER2- metastatic breast cancer who have progressed on endocrine therapy or premenopausal women receiving a luteinizing hormone-releasing hormone (LHRH) agonist.
Ibrance is an oral inhibitor of CDKs 4 and 6, which are key regulators of the cell cycle that trigger cellular progression. In the US, Ibrance is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.
Including the US, Ibrance is approved in more than 60 countries.