FDA approves IBRANCE® (palbociclib) with HER2-targeted and endocrine therapy for HR+/HER2+ metastatic breast cancer maintenance, supported by Phase 3 PATINA trial showing significant PFS benefit.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved IBRANCE® (palbociclib) in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adults with hormone receptor (HR)-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment. With this decision, IBRANCE becomes the first and only CDK4/6 inhibitor approved for patients with HR-positive metastatic breast cancer regardless of HER2 status.
IBRANCE Expands Treatment Options for HR+/HER2+ Disease
IBRANCE is an oral cyclin-dependent kinase (CDK) 4/6 inhibitor that blocks cell-cycle progression and suppresses cancer cell proliferation. Since its initial FDA approval in 2015, it has become a standard first-line therapy for HR-positive, HER2-negative advanced or metastatic breast cancer.
The new indication addresses an important unmet need in HR-positive, HER2-positive metastatic breast cancer, a subtype accounting for approximately 10% of breast cancer cases. Although HER2-targeted therapies have improved outcomes, resistance frequently develops during maintenance treatment, limiting long-term disease control.
PATINA Trial Showed Significant Progression-Free Survival Benefit
The approval is based on results from the global Phase 3 PATINA (AFT-38; NCT02947685) trial, a randomized, open-label study evaluating IBRANCE as first-line maintenance therapy after induction treatment in patients with HR-positive, HER2-positive metastatic breast cancer.
After receiving a median of six induction treatment cycles, 518 patients were randomized to receive either IBRANCE plus trastuzumab, with or without pertuzumab, and endocrine therapy (n=261), or anti-HER2 therapy with endocrine therapy alone (n=257). The primary endpoint was investigator-assessed progression-free survival (PFS).
Adding IBRANCE reduced the risk of disease progression or death by 24% compared with standard maintenance therapy (HR 0.76; 95% CI, 0.59-0.97; one-sided p=0.0134). Overall survival remains a secondary endpoint and the data are not yet mature.
The safety profile was consistent with previous studies of palbociclib. The most common adverse events were hematologic toxicities, including decreased white blood cell and neutrophil counts. Frequently reported non-hematologic adverse events included diarrhea, infections, stomatitis, and fatigue, most of which were mild to moderate in severity.
The PATINA findings were previously published in The New England Journal of Medicine and presented at the 2024 San Antonio Breast Cancer Symposium.
Experts Highlight New Maintenance Strategy
Pfizer said the approval expands the clinical role of IBRANCE across HR-positive metastatic breast cancer. Aamir Malik, Chief U.S. Commercial Officer and Executive Vice President at Pfizer, said the expanded indication reinforces CDK4/6 inhibition as a key component of combination therapy while addressing treatment resistance in HER2-positive disease.
Otto Metzger, MD, principal investigator of the PATINA trial for Alliance Foundation Trials and medical oncologist at Dana-Farber Cancer Institute, said resistance to dual HER2-targeted and endocrine therapy remains a major clinical challenge. He noted that adding IBRANCE during maintenance therapy can significantly extend the time patients remain free from disease progression and provides oncologists with a new evidence-based treatment option.
Clinical Significance
The PATINA trial is the first registrational study to demonstrate the benefit of CDK4/6 inhibition in HR-positive, HER2-positive metastatic breast cancer. With more than 900,000 patients treated worldwide and approvals in over 100 countries, IBRANCE continues to expand its role in metastatic breast cancer. The latest FDA approval introduces a new maintenance treatment option that integrates CDK4/6 inhibition with HER2-directed and endocrine therapies for patients with this difficult-to-treat subtype.
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About the Writer
Sana Jamil Khan (LinkedIn) is a B. Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.