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AboutAboutIBRANCE experienceMechanism of actionDosing & MonitoringDosing & MonitoringDosing and administrationMonitoringRecommended dose modifications for IBRANCEWhat you need to know about IBRANCE tabletsEfficacyEfficacyIBRANCE + aromatase inhibitorPrimary endpointSecondary endpointsUpdated analysesSubgroup analysesIBRANCE + fulvestrantPrimary endpointSecondary endpointsUpdated analysesSubgroup analysesSafety DataSafety DataIBRANCE + aromatase inhibitorAdverse reactionsDiscontinuations and dose reductionsNeutropenia and lab abnormalitiesWarnings and PrecautionsIBRANCE + fulvestrantAdverse reactionsDiscontinuations and dose reductionsNeutropenia and lab abnormalitiesWarnings and PrecautionsReal-World Evidence​​​​​​​Real-World EvidenceIntroductionRandomized controlled trialReal-world study designReal-world study patient characteristicsReal-world effectiveness dataLabelLinkLinkLinkLinkLabelLinkLinkLinkLinkSupport & OrderSupport &
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Expand here to viewReal-World Evidence

Randomized controlled trial summary

Real-world evidence can complement data from randomized controlled trials. It is important to understand both the randomized controlled trial results and the limitations of real-world evidence.

Review results from PALOMA-2, the randomized controlled trial that evaluated IBRANCE + letrozole in postmenopausal women with estrogen receptor-positive (ER+)/HER2- mBC and no prior treatment in the metastatic setting.1

Understand the Study Limitations (expand here to view)
  • This study is a retrospective database study of electronic health records, which may have missing data (e.g., ECOG baseline scores [~30%]) or erroneous data entry 
  • Patients were not randomly assigned. Treatments were selected by prescribing physician
  • A causal relationship between treatments and outcomes cannot be determined
  • While statistical analyses* were used to balance baseline and clinical patient characteristics, unobserved variables cannot be fully addressed through these methods. The analysis may not adequately adjust for all variables (e.g., interval from initial breast cancer diagnosis to mBC diagnosis)
  • This analysis may not adjust for all sources of potential bias (e.g., immortal time bias)
  • May not fully account for intercurrent events (e.g., dose modifications, titration, ancillary and concomitant therapies)
  • Findings presented here may not be generalizable to patient populations not represented in the Flatiron Database2
  • Safety data were not collected as part of the study
Statistical analyses included sIPTW as the primary analysis and PSM as the sensitivity analysis.

PALOMA-2 randomized controlled trial

Investigator-assessed progression-free survival (PFS)In combination with letrozole, IBRANCE delivered more than 2 years of median progression-free survival (mPFS) in first-line mBC1*Study design1

2:1 randomized, double-blind, Phase 3 trial studying IBRANCE + letrozole vs placebo + letrozole in postmenopausal women receiving first-line treatment for estrogen receptor-positive (ER+)/HER2- mBC (N=666)†

Primary endpoint1

Investigator-assessed progression-free survival (PFS)

  • 24.8 months of mPFS with IBRANCE + letrozole (n=444; 95% CI: 22.1-not estimable [NE]) vs 14.5 months with placebo + letrozole (n=222; 95% CI: 12.9-17.1); HR=0.58 (95% CI: 0.46-0.72); P<0.0001

  • Number of PFS events: 194 (43.7%) in the IBRANCE + letrozole arm and 137 (61.7%) in the placebo + letrozole arm

  • IBRANCE + letrozole reduced the risk of disease progression or death by 42% vs placebo + letrozole

Select secondary endpoints1,3
  • Objective response rate (ORR)‡: 55.3% (95% CI: 49.9-60.7) of patients with measurable disease achieved an objective response with IBRANCE + letrozole vs 44.4% (95% CI: 36.9-52.2) with placebo + letrozole (IBRANCE + letrozole n=338; placebo + letrozole n=171)
  • Overall survival (OS)§: A final OS analysis was conducted with 435 events (~65% of trial population) having occurred
    • OS was not statistically significant
    • Median OS was 53.8 months (95% CI: 49.8-59.2) with IBRANCE + letrozole vs 49.8 months (95% CI: 42.3-56.4) with placebo + letrozole (HR=0.92 [95% CI: 0.76-1.12]; P=0.2087)
ReferencesPO=by mouth.Unless otherwise stated, PALOMA-2 data are based on the February 2016 data cut (final prespecified analysis).1PALOMA-2 studied IBRANCE 125 mg PO once daily taken 3 weeks on, 1 week off + letrozole 2.5 mg PO once daily vs placebo + letrozole in postmenopausal women.1ORR was defined as the number (%) of patients with confirmed complete response or partial response.1November 2021 data cut.3Adverse reactions (ARs) reported in ≥10% of patients in PALOMA-2ReferencesGrading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.Infections include all reported preferred terms (PTs) that are part of the System Organ Class Infections and infestations; most common infections (≥1%) include nasopharyngitis, upper respiratory tract infection, urinary tract infection, oral herpes, sinusitis, rhinitis, bronchitis, influenza, pneumonia, gastroenteritis, conjunctivitis, herpes zoster, pharyngitis, cellulitis, cystitis, lower respiratory tract infection, tooth infection, gingivitis, skin infection, gastroenteritis viral, respiratory tract infection, respiratory tract infection viral, and folliculitis.In the IBRANCE + letrozole arm, 30% of patients had Grade 1 alopecia and 3% had Grade 2. In the placebo + letrozole arm, 15% of patients had Grade 1 alopecia and 1% had Grade 2.Stomatitis includes aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oral discomfort, oropharyngeal pain, and stomatitis.Rash includes the following PTs: rash, rash maculo-papular, rash pruritic, rash erythematous, rash papular, dermatitis, dermatitis acneiform, and toxic skin eruption.Updated non-prespecified analysis of PFS††

27.6 months of mPFS with IBRANCE + letrozole (n=444; 95% CI: 22.4-30.3) vs 14.5 months with placebo + letrozole (n=222; 95% CI: 12.3-17.1); HR=0.56 (95% CI: 0.46-0.69).4

  • Number of PFS events: 245 (55.2%) in the IBRANCE + letrozole arm and 160 (72.1%) in the placebo + letrozole arm3

Selected adverse events (AEs) reported in an updated non-prespecified analysis (with a median follow-up of 38 months) of PALOMA-24††

The most common selected AEs (≥10%, all causality)‡‡ of any grade reported in an updated non-prespecified analysis of PALOMA-2 for IBRANCE + letrozole vs placebo + letrozole were neutropenia (82% vs 6%), infections (63% vs 45%), leukopenia (40% vs 2%), fatigue (40% vs 28%), nausea (37% vs 27%), alopecia (34% vs 16%), stomatitis (32% vs 15%), diarrhea (28% vs 21%), anemia (26% vs 10%), rash (20% vs 13%), thrombocytopenia (20% vs 1%), asthenia (18% vs 12%), decreased appetite (17% vs 9%), vomiting (17% vs 17%), dry skin (13% vs 7%), pyrexia (13% vs 9%), alanine aminotransferase (ALT) increased (13% vs 6%), aspartate aminotransferase (AST) increased (12% vs 6%), and dysgeusia (10% vs 5%).

Selected AEs reported in the final OS analysis (with a median follow-up of 90 months) of PALOMA-23,5§§

The most common selected adverse events (≥10%, all causality)‡‡ of any grade reported in the final OS analysis of PALOMA-2 for IBRANCE + letrozole vs placebo + letrozole were neutropenia (82% vs 6%), infections (64% vs 46%), leukopenia (43% vs 3%), fatigue (41% vs 29%), nausea (38% vs 27%), alopecia (34% vs 16%), stomatitis (33% vs 15%), diarrhea (30% vs 23%), anemia (28% vs 10%), rash (22% vs 13%), thrombocytopenia (21% vs 2%), asthenia (19% vs 12%), decreased appetite (20% vs 10%), vomiting (18% vs 18%), dry skin (15% vs 7%), pyrexia (15% vs 9%), alanine aminotransferase increased (15% vs 6%), aspartate aminotransferase increased (14% vs 6%), and dysgeusia (NR vs NR).

In an updated non-prespecified PFS analysis and the final OS analysis, no new safety signals were observed.3-5

ReferencesNR=not reported.Based on May 2017 data cut (non-prespecified analysis), with a median follow-up of 38 months.4Incidences of AEs are all causality, and the AEs were selected based on their designation as ARs (treatment-related) in PALOMA-2 in the IBRANCE Prescribing Information.4Based on November 2021 data cut (final OS analysis), with a median follow-up of 90 months.3,4 Differences between randomized controlled trials and real-world evidence Take another look Loading NEXT: Real-world study design and study limitations Review this important context LoadingReferences:Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925-1936. doi:10.1056/NEJMoa1607303Rugo HS, Brufsky A, Liu X, et al. Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer. NPJ Breast Cancer. 2022;8(1):114. doi:10.1038/s41523-022-00479-xData on file. Pfizer Inc., New York, NY.Rugo HS, Finn RS, Diéras V, et al. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat. 2019;174(3):719-729. doi:10.1007/s10549-018-05125-4Finn RS, Rugo HS, Diéras V, et al. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ER+/HER2- ABC): analyses from PALOMA-2. Oral presentation at American Society of Clinical Oncology 2022 Annual Meeting; June 3-7, 2022; Chicago, IL.To view a copy of the license for Rugo HS, Brufsky A, Liu X, et al (NPJ Breast Cancer. 2022;8(1):114), please visit https://creativecommons.org/licenses/by/4.0/Real-World Evidence

Access the publication.
The FDA-approved Prescribing Information for IBRANCE includes data from the PALOMA clinical trials. However, some data reported in this publication may be different from, or are not included in, the IBRANCE Prescribing Information. Please review results from PALOMA-2 (RCT) provided on this page. The study met its primary endpoint of progression-free survival but did not meet the secondary endpoint of overall survival.

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Indications IBRANCE® (palbociclib) 125 mg capsules and tablets are indicated for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (mBC) in combination with:
 
  • an aromatase inhibitor as initial endocrine-based therapy, or
  • fulvestrant in patients with disease progression following endocrine therapy
Important Safety Information 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.
 

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), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no 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. 
 

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. 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. 

Please see full Prescribing Information for IBRANCE capsules and tablets.

IndicationsIBRANCE® (palbociclib) 125 mg capsules and tablets are indicated for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (mBC) in combination with:
  • an aromatase inhibitor as initial endocrine-based therapy, or
  • fulvestrant in patients with disease progression following endocrine therapy