• Prescribing Information for Capsules
  • Prescribing Information for Tablets
  • Patient Site
  • Medical Information
  • Pfizer recognizes the public concern in relation to COVID-19, which continues to evolve.

    Click here to learn how we are responding.

    Real-World Evidence

    Real-world study design

    Real-world evidence complements data from randomized clinical trials. It is important to understand both the randomized clinical trial results and the limitations of this observational retrospective real-world study.

    Expand here to view

    • Review results from PALOMA-2, the randomized clinical trial that evaluated IBRANCE + letrozole in postmenopausal women with estrogen receptor-positive (ER+)/HER2- mBC and no prior treatment in the metastatic setting
    • Understand the limitations of this observational retrospective real-world study: 
      • Observational retrospective database analyses cannot conclude causality, are not intended for direct comparison with randomized controlled trials or other real-world studies, may have missing data or erroneous data entry, and incomplete capture of comorbid conditions and performance status
      • Bias related to treatment selection and unobserved variables may confound these findings 
      • Disease progression was based on the individual treating physician’s clinical assessment or interpretation of radiographic or pathologic results and not on standard criteria, such as Response Evaluation Criteria in Solid Tumors (RECIST)
      • Significant censoring in the OS analysis highlights the need for subsequent evaluation with longer follow-up
      • Subsequent treatment may have impacted OS outcomes, and further research is warranted
      • Subgroup analyses are exploratory and are not sufficiently powered to detect significant differences
      • Findings from the Flatiron Health Analytic Database  should not be generalized to other patient populations 
      • Safety data were not collected as part of the study

    Observational retrospective analysis of EHRs of women with HR+/HER2- mBC receiving first-line IBRANCE + letrozole or letrozole alone1

    Objective1

    • To determine real-world effectiveness of first-line use of IBRANCE + letrozole vs letrozole alone in a cohort of women with HR+/HER2- mBC treated in routine clinical practice from across the United States

    Observational retrospective analyses are not intended 
    for direct comparison with clinical trials.

    Methodology1

    • Observational retrospective analysis of EHRs conducted using de-identified patient data from the Flatiron Health Analytic Database, which represents patients from across the United States
      • The Flatiron Health Analytic Database is a longitudinal database that includes structured and unstructured EHRs from >280 cancer clinics, including approximately 800 sites of care, and represents 2.4 million patients with cancer actively being treated in the United States

    Inclusion criteria1

    • Women aged ≥18 years at mBC diagnosis with HR+/HER2- mBC before or up to 60 days after the metastatic diagnosis date
    • A date of first prescription (index date) for IBRANCE + letrozole or letrozole alone as first-line therapy for mBC beginning on the date of the US FDA approval of IBRANCE, February 3, 2015, and extending 4 years to February 28, 2019
    • A minimum potential follow-up for ≥3 months from the index date to the study cutoff date of May 31, 2019*

    Exclusion criteria1​​​​​​​

    • Received prior treatment with CDK4/6 inhibitors, aromatase inhibitors, fulvestrant, tamoxifen, raloxifene, or toremifene in the metastatic setting
    • Had a first structured activity (a recording of vital information, a medication administration, a non-canceled drug order, or a reported laboratory test/result) >90 days after the mBC diagnostic date
    • Received a CDK4/6 inhibitor as part of a clinical trial

    Outcomes1 ​​​​​

    Real-world PFS (rwPFS) and OS were preplanned endpoints

    • Primary: rwPFS defined as time in months from start of IBRANCE + letrozole or letrozole alone to death or disease progression (determined by the recorded assessment of the treating clinician based on radiology, laboratory evidence, pathology, or clinical assessment)
    • Secondary: OS defined as number of months from start of IBRANCE + letrozole or letrozole alone to death due to any cause as recorded by Flatiron in the data extract

    Statistical analysis

    • Stabilized inverse probability treatment weighting (sIPTW) was applied to patients to balance baseline demographic and clinical characteristics between the 2 cohorts1
      • sIPTW is a statistical approach increasingly used in observational retrospective real-world studies where randomization is not possible. Patients are weighted differently in the sample to create 2 cohorts that have balanced characteristics across the 2 arms1,2
      • This approach was used as the primary analysis1
    • The Kaplan-Meier method and 95% CIs were used to estimate medians for rwPFS and OS1

    Study limitations1

    • Observational retrospective database analyses cannot conclude causality, are not intended for direct comparison with randomized controlled trials or other real-world studies, may have missing data or erroneous data entry, and incomplete capture of comorbid conditions and performance status
    • Bias related to treatment selection and unobserved variables may confound these findings
    • Disease progression was based on the individual treating physician’s clinical assessment or interpretation of radiographic or pathologic results and not on standard criteria, such as Response Evaluation Criteria in Solid Tumors (RECIST)
    • Significant censoring in the OS analysis highlights the need for subsequent evaluation with longer follow-up
    • Subsequent treatment may have impacted OS outcomes, and further research is warranted
    • Subgroup analyses are exploratory and are not sufficiently powered to detect significant differences
    • Findings from the Flatiron Health Analytic Database should not be generalized to other patient populations
    • Safety data were not collected as part of the study

        CDK4/6=cyclin-dependent kinases 4 and 6; EHR=electronic health record.

    *   The duration of follow-up was defined as the time in months from the start of IBRANCE + letrozole or letrozole alone to death or the data cutoff date of May 31, 2019, whichever came first. Median duration of follow-up was 24.2 months vs 23.3 months for patients who received IBRANCE + letrozole vs letrozole alone, respectively.1

       If patients did not die or have disease progression, they were censored at the date of initiation of next line of therapy for those with 2 or more lines of therapy or at their last visit during the study period (February 2015–May 2019) for patients with only 1 line of therapy.1

    ‡   If patients did not die, they were censored at the study cutoff date of May 31, 2019.1

    Review the randomized clinical trial information

    Take another look

    NEXT: Real-world study patient characteristics

    See the data


    References:
    1. DeMichele A, Cristofanilli M, Brufsky A, et al. Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2– metastatic breast cancer in US real-world clinical practice. Breast Cancer Res. Published online March 24, 2021. doi:10.1186/s13058-021-01409-8
    2. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34(28):3661-3679. 

    Real-World Evidence

    Get a copy of the real-world study brochure

    Download now

    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.

    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 in postmenopausal women or in men, or
    • fulvestrant in patients with disease progression following endocrine therapy

    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 in postmenopausal women or in men, or
    • fulvestrant in patients with disease progression following endocrine therapy