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

PALOMA-3 Trial Design

IBRANCE + fulvestrant in women with HR+/HER2- MBC whose disease progressed following endocrine therapy

Trial Design
Patient Characteristics

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

Primary endpoint1: Progression-free survival*
Secondary endpoints1,2: Overall response rate (ORR) and duration of response

PALOMA-3 HR+/HER2- MBC patient population included
Pre/-perimenopausal
Postmenopausal
First line
Later lines
Bone-only disease
Visceral disease
*Evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
ORR was defined as the number (%) of patients with complete response or partial response.2
Pre-/perimenopausal women enrolled in PALOMA-3 received the luteinizing hormone-releasing hormone (LHRH) agonist goserelin for at least 4 weeks prior to and for the duration of the trial.
IBRANCE + fulvestrant: Efficacy and Safety Profile

REFERENCES
1. Turner NC, Ro J, André F, et al. PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209-219.
2. Data on file. Pfizer Inc, New York, NY.
PALOMA-3 included a broad range of patients
PALOMA-3 included women with varying sites of disease, prior treatment histories, and regardless of menopausal status1,2

IBRANCE + fulvestrant
(n=347)
placebo + fulvestrant
(n=174)
Age, years
Median (min, max) 57 (30, 88) 56 (29, 80)
<65 (%) 75.2 75.3
≥65 (%) 24.8 24.7
Race (%)
White 72.6 76.4
Asian 21.3 17.8
Black or other 5.8 5.2
Menopausal status
Pre-/perimenopausal* 20.7 20.7
Postmenopausal 79.3 79.3
Disease site (%)
Visceral disease 59.4 60.3
Bone only 22.8 20.7
Other 17.8 19.0
Disease-free interval (%)
≤24 months 17.9 18.5
>24 months 79.1 76.6
Prior therapy (%)
Chemotherapy 72.3 79.3
Aromatase inhibitor 85.3 86.8
Tomoxifen 60.8 59.8
Prior lines of MBC therapy (%)
0 24.2 25.9
1 38.0 40.2
2 25.9 24.7
≥3 11.8 9.2

MBC=metastatic breast cancer.
*Pre-/perimenopausal women enrolled in PALOMA-3 received the luteinizing hormone-releasing hormone (LHRH) agonist goserelin for at least 4 weeks prior to and for the duration of the trial.
Other is defined as bone with other nonvisceral disease site or other disease site alone. Bone was the site of disease in 75.8% of patients in the IBRANCE + fulvestrant arm vs 74.1% in the placebo + fulvestrant arm.2
Palbociclib (IBRANCE) + fulvestrant
for postmenopausal women or for premenopausal women receiving an ovarian suppression with an LHRH agonist with HR+/HER2- MBC that has progressed on or after prior adjuvant or metastatic endocrine therapy (category 1)3§
HER2=human epidermal growth factor receptor 2; HR=hormone receptor; NCCN®=National Comprehensive Cancer Network®.
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.3
§If there is disease progression while on a CDK4/6 inhibitor + letrozole, there are no data to support an additional line of therapy with another palbociclib regimen.3
IBRANCE + fulvestrant:
Efficacy and Safety Profile
IBRANCE + letrozole:
PALOMA-1 and PALOMA-2 Patient Characteristics

REFERENCES
1. Turner NC, Ro J, André F, et al; PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209-219.
2. Data on file. Pfizer Inc, New York, NY.
3. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed April 28, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.