New Subgroup Analysis of LUX-Lung 1 Trial Suggests Afatinib Increases Progression-Free Survival in Advanced Lung Cancer Patients More Likely to Have EGFR Mutations

RIDGEFIELD, Conn., Dec. 9, 2010 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. announced that new data from a subgroup analysis of the phase IIb/III LUX-Lung 1 trial show that afatinib (BIBW 2992) reached a four-fold extension (4.4 months vs. 1.0 month for placebo) in progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients most likely to have an epidermal growth factor receptor (EGFR) mutation.(1)  The updated LUX-Lung 1 data will be presented at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The LUX-Lung 1 trial compared afatinib to placebo in 585 patients with advanced NSCLC whose disease progressed after receiving chemotherapy and a first-generation EGFR tyrosine kinase-inhibitor (TKI), gefitinib or erlotinib. In the study, afatinib did not extend the primary endpoint of overall survival in these advanced NSCLC patients.(2)  In addition, patients in the subgroup receiving afatinib did not have a statistically significant increase in overall survival compared to placebo. The authors concluded that the overall survival endpoint may have been confounded by the use of extensive subsequent systematic therapies.(2)  The subgroup included in the new analysis comprised two-thirds of all patients from the study (385/585) who were most likely to have EGFR mutations, as determined by clinical criteria based on their response to and duration of prior treatment with EGFR-TKIs.(1) These findings build upon the initial results from the LUX-Lung 1 clinical trial presented at the recent European Society for Medical Oncology (ESMO) meeting in Milan.(2)

The two most common side effects associated with treatment with afatinib in the LUX-Lung 1 trial were diarrhea (87% all grades, with 17% Grade 3) and rash/acne (79% all grades, with 14% Grade 3).  These side effects were usually well-managed by supportive care and dose reduction.(2)

"We continue to be encouraged by the findings of this study as we move toward personalized treatments," said principal investigator Vincent A. Miller, M.D., associate attending physician at Memorial Sloan Kettering Cancer Center, New York. "These data suggest that a certain subgroup of patients – those most likely to have EGFR mutations – may respond more positively with afatinib, and warrant further investigation."

As part of Boehringer Ingelheim's comprehensive and robust LUX clinical trial program, the phase III LUX-Lung 3 trial recently began to specifically investigate afatinib as a first-line treatment in patients with advanced NSCLC who have EGFR mutations.

About Afatinib

Afatinib is an investigational orally-administered irreversible inhibitor of both the EGFR and human epidermal receptor 2 (HER2) tyrosine kinases that is under development in several solid tumors including NSCLC, breast and head and neck cancer.  Afatinib is not approved by the FDA; its safety and efficacy have not been fully established.  

About Afatinib's Clinical Trial Program: LUX Trial Program

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

LUX-Lung 1 was a phase IIb/III trial that investigated afatinib plus best supportive care (BSC) versus placebo plus BSC in NSCLC patients who were previously treated with first-line chemotherapy and first-generation EGFR-TKIs, erlotinib or gefitinib.

LUX-Lung 2 is a phase II trial evaluating afatinib in NSCLC patients with EGFR mutations, either treatment naïve or after one line of chemotherapy.

In two ongoing global phase III trials, LUX-Lung 3 and LUX-Lung 6, the efficacy and safety of afatinib is compared to standard chemotherapy for first-line treatment of NSCLC patients with EGFR mutations in different geographical regions.

LUX-Lung 4 is a phase I/II trial of afatinib in NSCLC patients who have progressed after conventional EGFR-TKI treatment.  

Another trial, LUX-Lung 5, is a global phase III trial in patients previously treated with erlotinib or gefitinib. This is the first randomized phase III trial investigating whether patients who initially benefit from treatment with afatinib alone may further benefit from afatinib beyond progression when given in combination with chemotherapy.

About Lung Cancer

Lung cancer is the second most common cancer and kills more people than any other cancer.  In 2010, approximately 222,250 new cases of lung cancer will be diagnosed in the United States, with 157,300 Americans dying from the disease. NSCLC is the most common form of lung cancer, accounting for about 85 percent of all lung cancers.(3)  Lung cancer remains an area of high unmet need, especially in its advanced stages where it is particularly aggressive and patients have limited treatment options. There is no FDA-approved therapy for patients with advanced lung cancer who have failed chemotherapy and progressed after treatment with an EGFR-TKI.

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.

In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21 percent of net sales in its largest business segment, Prescription Medicines, on research and development.

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

References:

1. Miller et al. Subgroup analysis of LUX-Lung 1: A randomized phase III trial of afatinib (BIBW 2992) + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1-2 lines of chemotherapy and erlotinib or gefitinib. Oral presentation at Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, Dec. 10, 2010.
2. Miller et al. Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2 + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1–2 lines of chemotherapy and erlotinib or gefitinib (LUX-Lung 1). Abstract LBA1, European Society of Medical Oncology (ESMO) Congress, Milan, October 2010.
3. 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 Dec. 3, 2010.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.