Boehringer Ingelheim Initiates Phase III Clinical Trial With Afatinib in Advanced Breast Cancer

RIDGEFIELD, Conn. Dec. 8, 2010 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced the initiation of a phase III clinical trial in the United States to investigate one of its oncology pipeline compounds, afatinib* (BIBW 2992), for the treatment of patients with advanced (metastatic) breast cancer.  Afatinib is an investigational orally administered irreversible inhibitor of both the epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2) tyrosine kinases.  Afatinib is under development in several solid tumors including non-small cell lung cancer (NSCLC) and head and neck cancer.

The LUX-Breast 1 phase III trial is the first pivotal study to evaluate afatinib in breast cancer and represents an important milestone for Boehringer Ingelheim to broaden its oncology development activities beyond NSCLC and head and neck cancer.  LUX-Breast 1 is a global, open-label, randomized study in patients with advanced breast cancer after prior treatment with trastuzumab who have an over-expression of the HER2 protein (HER2-positive patients). The primary endpoint of the study evaluates whether treatment with afatinib can extend the lives of these patients before their cancer progresses (i.e., progression-free survival or PFS) as compared to continuing treatment with trastuzumab, when both are added to the standard chemotherapy treatment vinorelbine. Overall survival and safety are among the secondary endpoints that will be assessed in the trial.

"Based on results from our proof of concept studies for afatinib in breast cancer, we are pleased to advance this program into a pivotal phase III trial," said Christopher Corsico, M.D., M.P.H., U.S. medical director, Boehringer Ingelheim Pharmaceuticals, Inc.  "We are initiating this important trial together with a team of investigators around the world to assess the clinical utility of afatinib for women with metastatic breast cancer."

Breast cancer is the second-leading cause of cancer death in women after lung cancer.  An estimated 39,840 American women are expected to die from breast cancer in 2010.(1)  HER2-positive breast cancer is a particularly aggressive form of the disease and is associated with a greater risk of disease progression and death compared to women with HER2-negative tumors.(2)  It is thought that in approximately 30 percent of advanced breast cancer cases, women overexpress the HER2 protein.(3)

About Afatinib

The LUX trial program is a comprehensive and robust program that comprises more than 10 trials conducted across the globe, investigating afatinib in a variety of different solid tumor types.  

The decision to progress afatinib into a phase III trial in breast cancer was based on previous phase II data in advanced HER2-positive breast cancer patients whose cancer had progressed following treatment with trastuzumab.  Cutaneous adverse events and diarrhea were the most common side effects and were largely manageable.(4)

Advanced breast cancer, also known as metastatic breast cancer, refers to the stage of the disease when cancer cells have broken away from the primary breast cancer site and spread to other parts of the body via the bloodstream or lymphatic system.(5)

About Boehringer Ingelheim in Oncology

Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research program to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world's leading cancer centers, Boehringer Ingelheim is committed to discovering and developing novel cancer treatments. This commitment is underpinned by using advances in science to develop a range of targeted therapies in areas of medical need, including various solid tumors and hematological cancers.

The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition.  Afatinib is currently in phase III clinical development in NSCLC and breast cancer.  Apart from afatinib, Boehringer Ingelheim's late-stage oncology portfolio includes BIBF 1120,** also in phase III development for the treatment of patients in two different tumor types, advanced NSCLC and ovarian cancer.  BIBF 1120 is an orally administered investigational triple angiokinase inhibitor that targets three of the receptor tyrosine kinases shown to aid in the regulation of angiogenesis:  fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR).

In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing inhibitors of polo-like kinase 1 (Plk1), a protein that is involved in the processes of cell division. These molecules are in the earlier stages of clinical development.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.  

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

* Afatinib is an investigational compound; its safety and efficacy have not been fully established.

** BIBF 1120 is an investigational compound; its safety and efficacy have not been fully established.

References:

1. American Cancer Society.  Cancer Facts and Figures: 2010.  Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-026238.pdf.  Last accessed October 15, 2010.
2. Slamon D et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.  Science. 1987 Jan 9;235(4785):177-82.
3. Penault-Llorca, F et al.  Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer (MBC). J Clin Oncol. 2005 23: 764
4. Hicklish T et al.  Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor to Treat Patients with HER2-positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab, Poster 5060 presented at 32nd Annual San Antonio Breast Cancer Symposium. 9-13 December 2009, San Antonio, Texas.
5. National Cancer Institute Fact Sheet.  Metastatic Cancer: Questions and Answers.  Available at: http://www.cancer.gov/cancertopics/factsheet/sites-types/metastatic. Last accessed October 15, 2010.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.