Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. In PATINA, neutropenia was the most frequently reported adverse reaction with an incidence of 78%, and Grade ≥3 neutropenia was reported in 61% of patients receiving IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy. Based on laboratory findings, 93% had a decrease in neutrophil counts including 47% with Grade 3 and 3.1% with Grade 4. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Febrile neutropenia has been reported in 0.8% of patients exposed to IBRANCE in the PATINA study. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. In PATINA, 1% of IBRANCE-treated patients had ILD/pneumonitis of any grade and no Grade 3, 4, or fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g., hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

Serious adverse reactions occurred in 25% of patients in PATINA who received IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy. Serious adverse reactions in ≥1% of patients receiving IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy included infections (8%), headache and pyrexia (1.5% each), and femur fracture (1.2%).

Fatal adverse reactions occurred in 1.2% of patients in PATINA who received IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy including (0.4% each) death, hepatic hemorrhage, and sepsis.

The most common adverse reactions (≥20%) occurring in PATINA, including laboratory abnormalities, for IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy vs trastuzumab, with or without pertuzumab, and endocrine therapy were white blood cell decreased (94% vs 25%), neutrophil count decreased (93% vs 19%), creatinine increased (92% vs 87%), hemoglobin decreased (81% vs 47%), diarrhea (70% vs 37%), infections (64% vs 43%), platelet count decreased (59% vs 6%), stomatitis (44% vs 11%), aspartate aminotransferase increased (39% vs 25%), decreased calcium (39% vs 30%), alanine aminotransferase increased (38% vs 28%), decreased potassium (33% vs 17%), fatigue (32% vs 21%), alkaline phosphatase increased (31% vs 23%), nausea (30% vs 15%), asthenia (27% vs 21%), headache (26% vs 18%), rash (22% vs 17%), pruritus (21% vs 17%), and muscle spasms (20% vs 11%).

Other Clinical Trials Experience: venous thromboembolism has been reported as an adverse reaction following administration of IBRANCE.

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

HER2-Positive Metastatic Breast Cancer
 

IBRANCE® (palbociclib) 125 mg capsules and tablets are indicated in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with HR-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment.