Fulvestrant

IBRANCE is the first CDK4/6 inhibitor to show benefit in a large Phase 3 trial in first-line HR+, HER2+ metastatic breast cancer, in combination with anti-HER2 and endocrine therapy NEW YORK, NY, USA I December 12, 2024 I Pfizer Inc. (NYSE:PFE) and Alliance Foundation Trials, LLC (AFT) today announced results from the Phase 3 PATINA trial demonstrating that the addition of IBRANCE ® (palbociclib) to current standard-of-care first-line maintenance therapy (following induction chemotherapy) resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). In the study, which is sponsored by AFT, median PFS was 44.3 months (95% CI: 32.4-60.9) for patients treated with IBRANCE in combination with anti-HER2 therapy (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapy, and 29.1 months (95% CI: 23.3-38.6) for patients treated with anti-HER2 therapy and endocrine therapy alone [HR: 0.74 (95% CI, 0.58-0.94); unstratified 1-sided p= 0.0074]. This represents an extension in median PFS of over 15 months. Overall survival, a secondary endpoint, was not yet mature at the time of the analysis. These results are being presented during a late-breaking oral session (Abstract GS2-12) and highlighted in the press program at the 47th San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas. “PATINA is the first large Phase 3 study to show the benefit of CDK4/6 inhibition in HR-positive, HER2-positive metastatic breast cancer,” said Otto Metzger, M.D., principal investigator of the trial for Alliance Foundation Trials and Medical Oncologist at the Dana-Farber Cancer Institute. “These results support the potential of this maintenance treatment to slow disease progression and improve clinical outcomes in this patient population.” Approximately 10% of all breast cancers are HR+, HER2+ i , which is sometimes referred to as double-positive or triple-positive breast cancer. Despite advances in treatment, the development of resistance to anti-HER2 and endocrine therapy is a challenge, and novel therapeutic approaches are needed for HR+, HER2+ MBC. ii IBRANCE is not currently indicated for HR+, HER2+ MBC. “IBRANCE, the first CDK4/6 inhibitor, revolutionized the treatment of HR-positive, HER2-negative metastatic breast cancer, and has been prescribed to over 773,000 patients since its initial approval in 2015,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “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, and we look forward to discussing the results with regulatory authorities.” The safety and tolerability of IBRANCE in the PATINA study was consistent with its known safety profile in HR+, human epidermal growth factor receptor 2-negative (HER2-) MBC, and no new safety signals were identified. 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. 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 approved in more than 108 countries. Pfizer plans to share the results from PATINA with regulatory authorities. About the PATINA Trial PATINA (AFT-38) is a randomized, open-label 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 chemotherapy treatment) for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). While Pfizer is providing funding support for the trial, PATINA is sponsored by Alliance Foundation Trials, LLC (AFT) in collaboration with six international cancer research groups in the U.S., Germany, Italy, Spain, Australia, and New Zealand. Study participants who were previously treated with anti-HER2 therapy 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 is progression-free survival (PFS) as assessed by the investigator. Overall survival is a secondary endpoint. About IBRANCE ® (palbociclib) IBRANCE is an oral inhibitor of CDKs 4 and 6, iii which are key regulators of the cell cycle that trigger cellular progression. iv,v 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. The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here . About Alliance Foundation Trials (AFT) Alliance Foundation Trials, LLC (AFT) is a research organization that develops and conducts cancer clinical trials, working closely with the Alliance for Clinical Trials in Oncology (Alliance) scientific investigators, and its institutional member network, research collaborators, and non-NCI funding sources. AFT seeks to fulfill a shared vision with Alliance to reduce the impact of cancer on people by uniting a broad community of scientists and clinicians from many disciplines committed to discovering, validating and disseminating effective strategies for the prevention and treatment of cancer. Current AFT studies are funded by industry collaborators and the Patient-Centered Outcomes Research Institute (PCORI). For more information about AFT, please visit www.AllianceFoundationTrials.org . About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . i National Cancer Institute. Cancer Stat Facts: Female Breast Cancer Subtypes. https://seer.cancer.gov/statfacts/html/breast-subtypes.html#:~:text=Percent%20of%20Female,Unknown%20(6%25) . Accessed December 2024. ii Nature. Estrogen/HER2 receptor crosstalk in breast cancer: combination therapies to improve outcomes for patients with hormone receptor-positive/HER2-positive breast cancer iii IBRANCE (palbociclib) Prescribing Information . New York. NY: Pfizer Inc: 2023. iv Weinberg, RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329. v Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22. SOURCE: Pfizer

This year’s San Antonio Breast Cancer Conference yielded major clinical updates on some of the hottest areas of oncology, from VEGF bispecifics that hope to challenge Merck’s Keytruda on efficacy to oral protein degraders that may offer patients more convenience. There were also a handful of early-stage readouts from drugmakers big and small advancing new and improved takes on established mechanisms or sticking it out with approaches that others have left by the wayside. We’ve rounded up data from these presentations here. BeiGene reported early safety data for its CDK4 selective inhibitor on Thursday. CDK4/6 inhibitors work by inhibiting cell cycling, head of solid tumors Mark Lanasa told Endpoints News in an interview. Most of that inhibition is driven by the CDK4 component, while the CDK6 component can add hematologic toxicity, so selective targeting could help minimize side effects, he said. The Phase 1a trial comprises three cohorts testing BeiGene’s BGB-43395 alone and in doublets with fulvestrant and letrozole in people with advanced or metastatic solid tumors, including HR-positive/HER2-negative breast cancer. The most common side effects were gastrointestinal. Blood-related events like neutropenia (4.6%) and anemia (12.3%) were less common and mostly low-grade. Pfizer is also pursuing CDK4 selective inhibition with an asset called atirmociclib. Back in February, the pharma company told investors the drug is a potential successor to its CDK4/6 inhibitor Ibrance, with benefits including more “complete and continuous” target coverage. On Friday, Pfizer presented preliminary data showing atirmociclib plus letrozole attained a 61% confirmed objective response rate in 33 front-line HR-positive/HER2-negative metastatic breast cancer patients in a Phase 1/2a solid tumor study. There were two instances of grade 2 neutropenia and one case of grade 3 neutropenia. ALX Oncology is advancing an approach that drugmakers like Gilead Sciences have given up on due to safety concerns — targeting CD47. The South San Francisco-based biotech has a broad-ranging clinical program for its candidate, evorpacept, which covers non-Hodgkin lymphoma, multiple myeloma and urothelial cancers. On Tuesday, ALX unveiled results from a Phase 1/2b test of evorpacept plus Jazz Pharmaceuticals’ HER2-targeted bispecific antibody Ziihera in solid tumors, including metastatic breast cancer. In 21 patients with HER2-positive disease, the regimen reached a 33.3% confirmed ORR and 3.6 months of median progression-free survival. The response rates (20%) and PFS (1.9 months) were lower in 15 patients with HER2-low disease. Common side effects included fatigue, nausea and diarrhea, but there were no treatment-related deaths or non-infectious lung side effects, the company said.