Boehringer Ingelheim Pharmaceuticals, Inc
· Results from two Phase III studies (LUX-Lung 3 and LUX-Lung 6) add to the body of evidence supporting the importance of first-line treatment with afatinib in patients whose tumors express the EGFR exon 19 deletion mutation
· This data provide additional insight into the use of afatinib for EGFR mutation positive patients with common mutations
· A separate Phase III study (LUX-Lung 5) in patients whose non-small cell lung cancer (NSCLC) progressed after several treatments showed an improvement in progression-free survival when continuing afatinib with chemotherapy after the tumors stopped responding to afatinib alone
Ridgefield, CT, May 14, 2014 – Boehringer Ingelheim today announced new overall survival data of two Phase III clinical trials (LUX-Lung 3 and LUX-Lung 6). Patients with advanced non-small cell lung cancer (NSCLC) whose tumors have the most common epidermal growth factor receptor (EGFR) mutation (exon 19 deletion) lived longer if treated with first-line afatinib compared to chemotherapy. An oral presentation at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) on June 2nd (3:00 - 6:00 PM CDT, E Hall D2; Abstract #8004 scheduled for 4:00 - 4:12 PM) will discuss these data in more depth, providing further insights into their impact on clinical practice and patient care. Data from six other abstracts involving afatinib and other compounds in Boehringer Ingelheim’s oncology portfolio will also be presented or published at ASCO in Chicago, May 30-June 3.
Overall survival results
In the pooled analysis from two of the largest trials in this patient population, afatinib prolonged survival of lung cancer patients whose tumors have common EGFR mutations compared with standard chemotherapy by a median of 3 months (27.3 to 24.3 months) and significantly reduced the risk of death by 19% (HR=0.81, p=0.037). The most pronounced reduction in risk of death was 41% (HR=0.59, CI 0.45, 0.77) in patients whose tumors have the most common EGFR mutation (exon 19 deletion of the EGFR gene); for patients with the exon 21 (L8585R) mutation there was no impact on overall survival (HR=1.25, CI 0.92, 1.71). Exon 19 deletions occur with a frequency of approximately 48% in EGFR-mutant lung tumors. See abstract (#8004) for full details.
The analysis of the delay in tumor growth (progression-free survival) and adverse events associated with afatinib in comparison with standard chemotherapy were consistent with previously published results of the primary data from these two trials.
“Our lung cancer patients urgently need more treatments that can improve overall survival,” said Lecia V. Sequist, M.D., MPH, medical oncologist at Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School. “These results provide encouraging perspective about overall survival when patients whose tumors have the most common EGFR mutation are treated with afatinib.”
The LUX-Lung 3 Phase III clinical trial compared afatinib with chemotherapy (pemetrexed/cisplatin) as a first-line treatment in patients with advanced NSCLC with EGFR mutations. The LUX-Lung 6 Phase III clinical trial evaluated afatinib versus chemotherapy (gemcitabine/cisplatin) as a first-line treatment for Asian patients with advanced NSCLC with EGFR mutations.
Investigation of afatinib treatment beyond disease progression
Results from another Phase III study in NSCLC patients (LUX-Lung 5) also presented at ASCO met its primary endpoint by showing an improvement in progression-free survival (PFS) when continuing treatment with afatinib in combination with chemotherapy after the tumor started to grow on afatinib alone (treatment beyond progression). This Phase III study compared afatinib and paclitaxel versus investigator’s choice of chemotherapy alone in patients with late-stage NSCLC whose disease has progressed after afatinib alone and have also failed several treatments, including chemotherapy, erlotinib or gefitinib.
Those patients who continued afatinib treatment, with the addition of chemotherapy, after progressing on afatinib alone, had a further delay in tumor growth compared to the group who stopped afatinib treatment and received chemotherapy only (tumor growth was delayed by 5.6 months and 2.8 months respectively, p=0.003). This corresponded to a 40% reduction in risk of disease progression (HR=0.60). The most common adverse events in patients treated with afatinib and chemotherapy versus chemotherapy were diarrhea (53.8% vs. 6.7%), hair loss or alopecia (32.6% vs. 15%) and weakness or asthenia (27.3% vs. 28.3%). See abstract (#8019) for full details.
Berthold Greifenberg, M.D., vice president, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc. commented: “These findings provide additional insights into afatinib's potential in patients with advanced lung cancer and across different stages of treatment. We now know that lung cancer represents an array of diseases, and we are proud to be conducting research on afatinib in a variety of treatment settings that may ultimately expand treatment options for patients with this devastating disease.”
About Metastatic NSCLC and Common EGFR Mutations
In some people, genetic mutations lead to the constant activation of the EGFR protein, which is associated with uncontrolled cell division and the development and progression of NSCLC. Among patients diagnosed with NSCLC (the most common form of lung cancer), it is estimated that between 10 and 15% of Caucasians and approximately 40% of Asians have EGFR mutations – which in 90% of cases are one of the two most common EGFR mutations (exon 19 deletions or exon 21 L858R).
About Gilotrif® (afatinib) tablets
GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations.
GILOTRIF is an oral, once-daily kinase inhibitor that is designed to irreversibly bind and inhibit the following receptors: EGFR (ErbB1), HER2 (ErbB2) and ErbB4.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Bullous and Exfoliative Skin Disorders
Interstitial Lung Disease (ILD)
Combination with Vinorelbine in HER2 Positive Metastatic Breast Cancer
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers
USE IN SPECIFIC POPULATIONS
GF PROF ISI Apr 2014
For full prescribing information, including patient information, please click here. You can also visit www.gilotrif.com or contact Boehringer Ingelheim’s Medical and Technical Information (MTI) Unit at 1-800-542-6257.
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 discover and develop innovative cancer treatments. Working in close collaboration with the international scientific community and a number of the world’s leading cancer centers, Boehringer Ingelheim’s commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumors and hematological cancers. The current focus of late-stage research includes compounds in three areas: signal transduction inhibition, angiogenesis inhibition and cell-cycle kinase inhibition. The company is also evaluating a robust and growing pipeline of early-stage oncology compounds in areas including growth/survival signaling, immunotherapy and epigenetics.
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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 and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
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