Important Safety Information and Indications

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. 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. 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.

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 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.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. 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.

IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min).

Indications

IBRANCE is indicated for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (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

Dosing and Therapy Management

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Start IBRANCE when you start endocrine therapy

HER2=human epidermal growth factor receptor 2; HR=hormone receptor; MBC=metastatic breast cancer.

IBRANCE: once-daily oral dosing

Pill not actual size.

  • For additional details, please refer to the full Prescribing Information for fulvestrant

Administration considerations

IBRANCE should be taken with food. Patients should be encouraged to take their dose at approximately the same time each day
If the patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time
IBRANCE capsules should be swallowed whole (patients should not chew, crush, or open them prior to swallowing). Capsules should not be ingested if they are broken, cracked, or otherwise not intact

Substrates: Doses of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure

Inducers: Avoid concurrent use of strong CYP3A inducers

Inhibitors: Avoid concurrent use of strong CYP3A inhibitors

–  If the strong inhibitor cannot be avoided, reduce the IBRANCE dose to 75 mg once daily

–  If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3 to 5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong inhibitor

–  Patients should avoid grapefruit or grapefruit juice during IBRANCE treatment

Pre-/perimenopausal women treated with the combination IBRANCE + fulvestrant therapy should be treated with LHRH agonists according to current clinical practice standards

LHRH=luteinizing hormone-releasing hormone.

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Proactively monitor patients to help manage potential side effects

Monitor the complete blood count (CBC) prior to the start of IBRANCE therapy and at the beginning of each cycle, as well as on Day 15 of the first 2 cycles, and as clinically indicated

When scheduling Day 15 monitoring and subsequent follow-up visits, remember to consider when the patient actually receives her medication and initiates each cycle.

Detecting and managing neutropenia

  • Neutropenia was the most frequently reported adverse event in PALOMA-1 (75%), PALOMA-2 (80%), and PALOMA-3 (83%). Grade ≥3 neutropenia was reported in 62% and 66% of patients receiving IBRANCE + letrozole in PALOMA-1 and PALOMA-2, respectively, and in 66% of patients receiving IBRANCE + fulvestrant in PALOMA-31
  • Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia
  • Per the US Prescribing Information, febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE. One death due to neutropenic sepsis was observed in the PALOMA clinical trials1
  • Advise patients to immediately report any signs or symptoms of myelosuppression or infection, such as fever, chills, dizziness, shortness of breath, weakness, or any increased tendency to bleed and/or to bruise
  • Primary prophylactic use of granulocyte-colony stimulating factors (GCSFs) was not permitted in PALOMA-1, PALOMA-2, or PALOMA-3, but they could be used to treat treatment-emergent neutropenia, as indicated by the current American Society of Clinical Oncology guidelines2

*Based on PALOMA-2 and PALOMA-3 data.

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IBRANCE + fulvestrant: Safety Profile

REFERENCES

1. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925-1936.

2. Data on file. Pfizer Inc, New York, NY.

Modify the dose if needed based on individual safety and tolerability

  • Dose modifications may help manage hematologic and nonhematologic toxicities, if they occur
  • For Grade 1 (ANC <LLN-1500/mm3) and Grade 2 (ANC 1000-<1500/mm3) hematologic and nonhematologic toxicities, no dose adjustment is required

Refer to the full Prescribing Information for coadministered endocrine therapy dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications.

Recommended dose modifications for IBRANCE
Starting doseFirst reductionSecond reduction
125 mg/day
100 mg/day
75 mg/day
If dose reduction below 75 mg/day is required, discontinue IBRANCE.

Pills not actual size.

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