Pfizer and Alliance Foundation Trials, LLC (AFT) have announced positive results from the Phase 3 PATINA trial, revealing that the addition of Ibrance (palbociclib) to standard-of-care first-line maintenance therapy significantly extends progression-free survival (PFS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). The study, sponsored by AFT, highlights a clinically meaningful improvement, offering new hope for patients with this aggressive form of breast cancer. These results were presented at the 47th San Antonio Breast Cancer Symposium (SABCS).
In the PATINA trial, patients treated with Ibrance in combination with anti-HER2 therapy (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapy achieved a median PFS of 44.3 months (95% CI: 32.4-60.9), compared to 29.1 months (95% CI: 23.3-38.6) for those treated with anti-HER2 therapy and endocrine therapy alone. This represents an extension in median PFS of over 15 months (HR: 0.74 (95% CI, 0.58-0.94); unstratified 1-sided p= 0.0074).
Clinical Significance
Otto Metzger, M.D., principal investigator of the trial for Alliance Foundation Trials and Medical Oncologist at the Dana-Farber Cancer Institute, emphasized the importance of these findings, stating, "PATINA is the first large Phase 3 study to show the benefit of CDK4/6 inhibition in HR-positive, HER2-positive metastatic breast cancer. These results support the potential of this maintenance treatment to slow disease progression and improve clinical outcomes in this patient population."
Disease Context and Unmet Needs
Approximately 10% of all breast cancers are HR+, HER2+, often referred to as double-positive or triple-positive breast cancer. Despite advancements in treatment, resistance to anti-HER2 and endocrine therapy remains a significant challenge, creating a need for novel therapeutic approaches. Ibrance is not currently indicated for HR+, HER2+ MBC, making these findings particularly relevant for future treatment strategies.
Safety and Tolerability
The safety and tolerability profile of Ibrance in the PATINA study was consistent with its established safety profile in HR+, HER2- MBC. The most common adverse events observed with Ibrance were hematologic toxicities, such as neutropenia and leukopenia. Non-hematologic adverse events included fatigue, stomatitis, and diarrhea, which were generally mild to moderate in severity. Grade 3 neutropenia was observed in 63.2% of patients in the palbociclib arm.
Trial Design and Endpoints
The PATINA trial (AFT-38) is a randomized, open-label Phase 3 study designed to evaluate the efficacy and safety of Ibrance 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 chemotherapy. The primary endpoint was progression-free survival (PFS) as assessed by the investigator, with overall survival as a secondary endpoint. The study enrolled 518 patients who were previously treated with anti-HER2 therapy.
Future Directions
Pfizer plans to discuss the results from PATINA with regulatory authorities, potentially paving the way for a new indication for Ibrance in HR+, HER2+ metastatic breast cancer. Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer, noted, "These results demonstrate that the addition of IBRANCE to standard of care shows promise as maintenance therapy in HR-positive, HER2-positive disease. PATINA underscores Pfizer’s ongoing commitment to addressing the unmet needs of people with breast cancer."
