On September 24, 2019 Pfizer Inc. (NYSE: PFE) reported the presentation of four IBRANCE (palbociclib) real-world analyses (Press release, Pfizer, SEP 24, 2019, View Source [SID1234539737]). The studies support the effectiveness of IBRANCE combination therapy in everyday clinical practice and provide additional insights on its use in certain patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The posters will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain on Sunday, September 29.
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Among the data, Pfizer will share the first real-world comparative analysis of a CDK 4/6 inhibitor in combination with an aromatase inhibitor compared to an aromatase inhibitor alone.
"We have an opportunity to make positive changes in cancer care by incorporating learnings from real-world data in addition to data gathered from clinical trials," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "We are pleased to share this view of the impact IBRANCE has had on patients treated outside of traditional clinical studies, as it continues to add to the body of evidence for IBRANCE and provides insights into the patient experience."
About the Real-World Comparative Analysis
In this retrospective analysis (Abstract #329P: Comparative effectiveness of palbociclib plus letrozole vs. letrozole for metastatic breast cancer in U.S. real-world clinical practices), treatment with IBRANCE plus letrozole demonstrated a statistically significant improvement in real-world progression-free survival (rwPFS) compared to letrozole alone: 24.5 months (95% CI = 20.7 – 32.7) versus 17.1 months (95% CI = 13.7 – 19.8) (HR = 0.68, 95% CI = 0.56 – 0.84, p = 0.0003).
"To help deliver the best care to our patients, it is critical that physicians have compelling evidence of a medicine’s benefit on patients who resemble those who they treat every day," said Rachel Layman, M.D., Associate Professor, Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center. "The real-world evidence presented at ESMO (Free ESMO Whitepaper) provides a more robust understanding of the effectiveness of IBRANCE in patients who may not be reflected in the randomized trials."
The analysis compared 906 matched patients with HR+, HER2- MBC who started IBRANCE plus letrozole as initial endocrine-based therapy in the metastatic setting (n=453) or letrozole alone (n=453) from February 2015 to August 2018. rwPFS was measured by the treating physician’s clinical assessment of source evidence, such as radiographic scans or pathology from the Flatiron Health longitudinal database. The most recent update for this database includes de-identified electronic health records from more than 280 cancer clinics representing more than 2.2 million cancer patients in the U.S.
The additional real-world posters at ESMO (Free ESMO Whitepaper) examining the use of IBRANCE in patients with HR+, HER2- MBC are:
Abstract #327P: Palbociclib plus an aromatase inhibitor as first-line therapy for metastatic breast cancer in U.S. clinical practices: Real-world progression-free survival analysis
This single-arm analysis of real-world disease progression and overall survival rates in patients treated with IBRANCE plus an aromatase inhibitor (AI), also from the Flatiron database, examined the use of IBRANCE combination therapy as initial treatment for patients with HR+, HER2- MBC.
Abstract #338P: Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the U.S.
An analysis of clinical effectiveness of IBRANCE plus letrozole in patients who began treatment on or after February 2015, using the Cardinal Health Oncology Provider Extended Network.
Abstract #365P: Measures of functional status in adults aged >70 years with advanced breast cancer receiving palbociclib combination therapy in POLARIS
A subgroup analysis from the ongoing prospective, observational POLARIS study provides insights into the use of IBRANCE in geriatric patients (age 70 or older) treated in everyday clinical practice – a population for which limited data are available.
To further educate the global oncology community about the importance of real-world data at ESMO (Free ESMO Whitepaper), Pfizer is sponsoring a satellite symposium, Real World Data in Oncology: Its Growing Role in Research and Patient Care. The symposium will take place on Friday, September 27, from 6:00 – 8:00 pm CEST at Fira Gran Via in the Alicante Auditorium (Hall 3).
About IBRANCE (palbociclib) 125 mg capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is 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 in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.
The most common adverse reactions (incidence ≥10%) associated with IBRANCE are neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anemia, alopecia, diarrhea, thrombocytopenia, rash, vomiting, decreased appetite, asthenia, and pyrexia. Today in the U.S., IBRANCE is the most prescribed FDA-approved oral combination treatment for HR+, HER2- metastatic breast cancer.
IBRANCE currently is approved in more than 90 countries and has been prescribed to more than 230,000 patients globally.
The full U.S. Prescribing Information for IBRANCE can be found here.
IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING 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.