May 29, 2020: “Pfizer announced by the Austrian Breast & Colorectal Cancer Study Group and the Alliance Foundation Trials, LLC, Pfizer Inc. reports that following a preplanned efficacy and futility analysis, the independent Data Monitoring Committee (DMC) of the collaborative Phase 3 early breast cancer PALbociclib CoLlaborative Adjuvant Study (PALLAS) determined that the trial is unlikely to show a statistically significant improvement in the primary endpoint of invasive disease-free survival (iDFS).
Patients currently receiving palbociclib in the study will be advised about next steps by their physicians and long-term follow up of all patients will proceed as planned. No unexpected new safety signals were observed in patients receiving palbociclib.
The PALLAS trial compares palbociclib plus standard adjuvant endocrine therapy to standard adjuvant endocrine therapy alone in women and men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early (stage 2 and 3) breast cancer and is an academically-led global collaboration, involving more than 400 centres in 21 countries around the globe.
“We are disappointed in this outcome. Breast cancer is a leading cause of death around the world and delaying or preventing the development of metastatic disease is a significant unmet need.
PALLAS is a large study with many subgroups and we are actively collaborating to determine if there are patients who may benefit from adjuvant treatment with the palbociclib combination,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development.
“Since its initial approval in 2015, IBRANCE has helped change the treatment landscape for people with HR+, HER2- metastatic breast cancer. We are grateful to all patients, health care providers and our academic partners who have devoted so much to make this important study possible.”
“This result is not what we hoped for, but we are steadfast in our commitment to advancing the science and care for people living with breast cancer,” said Albert Bourla, Pfizer Chairman and CEO.
“Given the continued breadth of our marketed portfolio and strength of our pipeline, our growth projections are not reliant upon any individual marketed medicine or pipeline opportunity.
Consequently, we remain highly confident in our ability to deliver, following the closing of the proposed combination of Upjohn with Mylan N.V., a compound annual growth rate for revenues of at least 6% through 2025.”
Health authorities and trial investigators have been notified of this decision. When available, the full results from the PALLAS study will be shared with the scientific community at a later date.
Palbociclib is also being studied in patients with high-risk early breast cancer and results from the collaborative PENELOPE-B trial are expected later this year.
In the U.S., IBRANCE is approved for the treatment of adult patients with HR+, 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.
IBRANCE is not indicated in early breast cancer. The collaborative Phase 3 PENELOPE-B study (NCT01864746) continues to explore the potential of IBRANCE in patients with early breast cancer at high risk of recurrence who have residual disease after neoadjuvant chemotherapy.
PALLAS Trial
PALLAS is a randomized (1:1), prospective, international, multicenter, open-label Phase 3 study comparing the combination of palbociclib and standard adjuvant endocrine therapy for two years followed by continuing standard adjuvant therapy to complete five years versus at least five years of standard adjuvant endocrine therapy for pre- and postmenopausal women or men with HR+, HER2- early invasive (Stage 2 and Stage 3) breast cancer, including those at moderate to high risk of recurrence.
The trial is co-sponsored by the Austrian Breast & Colorectal Cancer Study Group and the Alliance Foundation Trials as part of a clinical research collaboration with Pfizer and other study groups, including PrECOG, LLC; NSABP Foundation Inc; and the Breast International Group (BIG).
IBRANCE® (palbociclib) 125 mg tablets and capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6, which are key regulators of the cell cycle that trigger cellular progression
In the U.S., IBRANCE is indicated for the treatment of adult patients with HR+, 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.
IBRANCE currently is approved in more than 95 countries and has been prescribed to more than 300,000 patients globally.
The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and 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.”
