The following topics are described below and elsewhere in the labeling:
- Neutropenia [see WARNINGS AND PRECAUTIONS]
- Infections [see WARNINGS AND PRECAUTIONS]
- Pulmonary Embolism [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience
Because clinical trials are conducted under varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
The safety of IBRANCE (125 mg/day) plus letrozole (2.5 mg/day) versus letrozole alone was evaluated in Study 1. The data described below reflect exposure to IBRANCE in 83 out of 160 patients with ER-positive, HER2-negative advanced breast cancer who received at least 1 dose of treatment in Study 1. The median duration of treatment for palbociclib was 13.8 months while the median duration of treatment for letrozole on the letrozole-alone arm was 7.6 months.
Dose reductions due to an adverse reaction of any grade occurred in 36% of patients receiving IBRANCE plus letrozole. No dose reduction was allowed for letrozole in Study 1.
Permanent discontinuation due to an adverse reaction occurred in 7 of 83 (8%) patients receiving IBRANCE plus letrozole and in 2 of 77 (3%) patients receiving letrozole alone. Adverse reactions leading to discontinuation for those patients receiving IBRANCE plus letrozole included neutropenia (6%), asthenia (1%), and fatigue (1%).
The most common adverse reactions ( ≥ 10%) of any grade reported in patients in the IBRANCE plus letrozole arm were neutropenia, leukopenia, fatigue, anemia, upper respiratory infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.
The most frequently reported serious adverse reactions in patients receiving IBRANCE plus letrozole were pulmonary embolism (3 of 83; 4%) and diarrhea (2 of 83; 2%).
An increase incidence of infections events was observed in the palbociclib plus letrozole arm (55%) compared to the letrozole alone arm (34%). Febrile neutropenia events have been reported in the IBRANCE clinical program, although no cases were observed in Study 1. Grade ≥ 3 neutropenia was managed by dose reductions and/or dose delay or temporary discontinuation consistent with a permanent discontinuation rate of 6% due to neutropenia [see DOSAGE AND ADMINISTRATION].
Adverse drug reactions ( ≥ 10%) reported in patients who received IBRANCE plus letrozole or letrozole alone in Study 1 are listed in Table 4.
Table 4: Adverse Reactions* ( ≥ 10%) in Study 1
|System Organ Class
|IBRANCE + Letrozole
|All Grades %||Grade 3 %||Grade 4%||All Grades %||Grade 3 %||Grade 4 %|
|Infections and infestations|
|Blood and lymphatic system disorders|
|Metabolism and nutrition disorders|
|Nervous system disorders|
|Respiratory, thoracic and mediastinal disorders|
|Skin and subcutaneous tissue disorders|
|General disorders and administration site conditions|
|*Adverse Reaction rates reported in the table include all reported events regardless of causality.
Grading according to CTCAE Version 3.0.
CTCAE=Common Terminology Criteria for Adverse Events; N=number of subjects; N/A=not applicable; URI=Upper respiratory infection.
a URI includes: Influenza, Influenza like illness, Laryngitis, Nasopharyngitis, Pharyngitis, Rhinitis, Sinusitis, Upper respiratory tract infection.
b Peripheral neuropathy includes: Neuropathy peripheral, Peripheral sensory neuropathy.
c Stomatitis includes: Aphthous stomatitis, Cheilitis, Glossitis, Glossodynia, Mouth ulceration, Mucosal inflammation, Oral pain, Oropharyngeal discomfort, Oropharyngeal pain, Stomatitis.
d Grade 1 events - 21%; Grade 2 events - 1%.
e Grade 1 events - 3%.
Table 5: Laboratory Abnormalities for Patients in Study 1
|Laboratory Abnormality||IBRANCE + Letrozole
|All Grades %||Grade 3 %||Grade 4 %||All Grades %||Grade 3 %||Grade 4 %|
|White blood cells||95||44||0||26||0||0|
|decreased Neutrophils decreased||94||57||5||17||3||0|
|N=number of patients.|