Announcement • 9h
Pfizer Inc Receives U.S. Food and Drug Administration Approval For IBRANCE Regimen For HR+, HER2+ Metastatic Breast Cancer Frontline Maintenance
Pfizer Inc. had the U.S. Food and Drug Administration (FDA) approve IBRANCE (palbociclib) in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) locally advanced or metastatic breast cancer (MBC) following induction treatment. The approval is based on positive results from the Alliance Foundation Trials, LLC (AFT)-sponsored Phase 3 PATINA trial. The PATINA trial demonstrated a 24% reduction in the risk of progression or death following induction treatment with the addition of IBRANCE to anti-HER2 (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapies compared to anti-HER2 and endocrine therapies alone (HR: 0.76 [95% CI, 0.59, 0.97]; one-sided p=0.0134). The safety and tolerability of IBRANCE in PATINA were consistent with its known safety profile. The most commonly reported adverse events with IBRANCE were hematologic toxicities, such as white blood cell decreased and neutrophil count decreased. Non-hematologic adverse events included diarrhea, infections, stomatitis, and fatigue, which were generally mild to moderate in severity. Results from the trial were previously published by AFT in the New England Journal of Medicine and presented at the 2024 San Antonio Breast Cancer Symposium. Approximately 10% of all breast cancers are HR+, HER2+, which is sometimes referred to as double-positive or triple-positive breast cancer. Historically, there has been limited research specifically focused on the HR+, HER2+ subtype in MBC, and PATINA is the first registrational study to explore the potential of CDK4/6 inhibition in this subtype. Since its initial regulatory approval in 2015, IBRANCE continues to be a standard-of-care first-line treatment for HR+, HER2- MBC and has been prescribed to more than 900,000 patients and approved in more than 100 countries. PATINA (AFT-38) was a randomized, open-label global Phase 3 study to evaluate the efficacy and safety of IBRANCE (palbociclib) in combination with anti-HER2 therapy (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapy compared to anti-HER2 therapy and endocrine therapy alone as a first-line maintenance therapy (following induction treatment) for patients with HR+, HER2+ MBC. Study participants who received a median of 6 cycles of induction treatment were randomized to receive IBRANCE, in addition to anti-HER2 therapy and endocrine therapy (n=261), or anti-HER2 therapy and endocrine therapy alone (n=257). The primary endpoint was progression-free survival (PFS) as assessed by the investigator. Overall survival is a secondary endpoint and is not yet mature. 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; or with fulvestrant in patients with disease progression following endocrine therapy. IBRANCE is indicated in combination with inavolisib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. IBRANCE is also indicated in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with HR-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment. 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. In PATINA, neutropenia was the most frequently reported adverse reaction with an incidence of 78%, and Grade =3 neutropenia was reported in 61% of patients receiving IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy. Based on laboratory findings, 93% had a decrease in neutrophil counts including 47% with Grade 3 and 3.1% with Grade 4. 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. Febrile neutropenia has been reported in 0.8% of patients exposed to IBRANCE in the PATINA study. 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% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. In PATINA, 1% of IBRANCE-treated patients had ILD/pneumonitis of any grade and no Grade 3, 4, or fatal cases were 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.