RIDGEFIELD, Conn., May 15, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) today announced data from two Phase III clinical trials involving two different investigational oncology compounds – afatinib* and nintedanib* – in two distinct patient populations with advanced non-small cell lung cancer (NSCLC). Results from both studies will be presented at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, May 31-June 4, 2013.
- Afatinib was evaluated in the LUX-Lung 6 trial as a first-line treatment in Asian patients with epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC. Patients treated with afatinib lived for almost a year before their tumor started to grow again (progression-free survival [PFS], the primary endpoint) as compared with just under half a year for patients treated with gemcitabine/cisplatin.
- Nintedanib was evaluated in combination with pemetrexed in the LUME-Lung 2 trial as a second-line treatment in patients with advanced NSCLC after first-line initial chemotherapy had failed. The study enrollment was halted based on an interim futility analysis. Based on the available data from 713 patients enrolled, an increased PFS was observed in patients treated with the nintedanib combination versus pemetrexed alone.
"The findings from these Phase III trials demonstrate the importance of exploring treatment approaches tailored for the various NSCLC patient populations," said Berthold Greifenberg, MD, vice president, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc. "These important studies demonstrate our commitment to researching new therapies for patients with this devastating disease. Afatinib and nintedanib are two investigational compounds in our growing oncology pipeline."
The LUX-Lung 6 Clinical Trial of Afatinib
LUX-Lung 6 (Efficacy) Abstract: #8016
Poster Discussion: Sunday, June 2, 11:30 AM-12:30 PM, poster board #5
The LUX-Lung 6 trial is the largest randomized, open-label Phase III trial conducted to date in the EGFR mutation-positive advanced (stage IIIb or IV) NSCLC patient population. The trial evaluated afatinib compared to standard chemotherapy (gemcitabine and cisplatin), as a first-line treatment in 364 Asian patients.1
The trial met its primary endpoint of PFS as assessed by independent central review; within the general study population, patients treated with afatinib (n=242) lived for a median of 11.0 months before their tumor started to grow again versus 5.6 months for patients treated with chemotherapy (n=122) (HR=0.28, p<0.0001).1 The PFS findings were consistent across EGFR mutation sub-groups.1 Secondary efficacy endpoints included objective response rate (ORR: proportion of patients with tumor size reduction of a predefined amount and for a minimum time period3) and disease control rate (DCR: proportion of patients who have achieved complete response, partial response and stable disease4). Patients treated with afatinib experienced significantly higher ORR (66.9% versus 23.0%, p<0.0001) and DCR (92.6% versus 76.2%, p<0.0001) compared to patients treated with chemotherapy.1
The most common greater than or equal to grade 3 drug-related adverse events observed in the afatinib treatment arm were rash/acne (14.6%), diarrhea (5.4%) and stomatitis/mucositis (5.4%).1 The most common greater than or equal to grade 3 drug-related adverse events observed in the gemcitabine/cisplatin treatment arm were neutropenia (17.7%), vomiting (15.9%) and leukopenia (13.3%).1 Overall, 5.9 percent of patients treated with afatinib discontinued treatment compared with 39.8 percent of patients treated with chemotherapy.1
LUX-Lung 6 (Patient-Reported Outcomes) Abstract: #8061
Poster: Saturday, June 1, 8:00-11:45 AM, poster board #35A
Patient-reported outcomes (PROs) were also evaluated as secondary endpoints of the LUX-Lung 6 trial and included analyses of health-related quality of life (QoL) and lung cancer-related symptoms compared with chemotherapy.
The analysis of lung cancer-related symptoms – cough, dyspnea (shortness of breath) and pain – was conducted using the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire for lung cancer (QLQ-LC13).5 Results showed:
- A higher proportion of patients in the afatinib arm, compared with those in the chemotherapy arm, reported 10 point or more improvements in cough (76% versus 55%; p=0.0003), dyspnea (71% versus 48%; p<0.0001) and pain (64% versus 47%; p=0.003)5
- Afatinib-treated patients experienced a significant delay in the worsening (time to deterioration) of cough (HR=0.45; p=0.0001), dyspnea (HR=0.54; p<0.0001) and pain (HR=0.70; p=0.03) compared to those treated with chemotherapy5
Health-related QoL was evaluated using the EORTC QLQ-C30 questionnaire, which evaluated global health status/QoL (overall well-being) in addition to physical, cognitive, role, social and emotional functioning.6 Based on these measures, afatinib-treated patients experienced improvements in their global health-related QoL (p<0.0001) and physical (p<0.0001), role (p=0.01) and social (p<0.001) functioning compared to chemotherapy.5
A significantly higher proportion of afatinib-treated patients had worsening of diarrhea, sore mouth and dysphagia; while fatigue, nausea and vomiting were significantly worse with gemcitabine/cisplatin.5
"These data from the LUX-Lung 6 trial add to the growing body of knowledge for the investigational compound, afatinib, in EGFR mutation-positive advanced non-small cell lung cancer," said William Goeckeler, PhD, director, Oncology Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "This is the second Phase III trial involving afatinib in this patient population to meet its primary efficacy endpoint and to incorporate health-related quality of life measures into the study design."
The LUME-Lung 2 Clinical Trial of Nintedanib
LUME-LUNG 2 (Efficacy) Abstract: #8034
Poster Discussion: Sunday, June 2, 11:30 AM-12:30 PM, poster board #23
This randomized, double-blinded Phase III study evaluated nintedanib plus pemetrexed compared to pemetrexed plus placebo in patients with advanced non-squamous NSCLC not responding to, or who progressed after, first-line chemotherapy.2 LUME-Lung 2 was halted at the recommendation of the Independent Data Monitoring Committee after 713 patients had been enrolled. This decision was based on the results of an interim review of efficacy (PFS) for a pre-defined futility analysis, and was not safety related. At the point of the interim review, PFS did not appear significantly improved compared to the comparator arm.
Data will be presented on the 713 patients who enrolled; results showed that the addition of nintedanib to pemetrexed improved PFS (HR=0.83, p=0.04) even though enrollment was stopped prematurely.2 Patients treated with nintedanib plus pemetrexed (n=353) lived for a median of 4.4 months before their tumor started to grow again (PFS), compared to 3.6 months for patients assigned to the pemetrexed plus placebo arm (n=360).2
A higher incidence of greater than or equal to grade 3 elevated ALT (23% versus 7%) and AST (12% versus 2%)2 – which are types of enzymes measured to determine liver health – as well as diarrhea (3% versus 1%) were observed in patients treated with nintedanib plus pemetrexed.2 Hypertension, bleeding, thrombosis, mucositis and neuropathy (greater than or equal to grade 3) were comparable between the two treatment arms.2 No increase in serious adverse events or grade five adverse events was observed in patients who received the combination of nintedanib plus pemetrexed.2
This study is part of the comprehensive LUME-Lung clinical trial program that is investigating nintedanib in different lung cancer treatment settings. Results from a second trial in the nintedanib LUME-Lung program will be presented on June 3 at ASCO.
About NSCLC and EGFR Mutations
NSCLC is the most common form of lung cancer, accounting for about 85 percent of all diagnoses.8 Between 10 and 15 percent of Caucasians and approximately 40 percent of Asians with NSCLC have EGFR mutations9 – 90 percent of which are the result of two mutations (Del19 or L858R).10
Afatinib is an investigational, oral, once-daily irreversible ErbB Family Blocker that specifically inhibits epidermal growth factor receptor (EGFR or ErbB1), human epidermal receptor 2 (HER2 or ErbB2) and ErbB4. It is currently in Phase III clinical development in advanced NSCLC and head and neck cancer. The company has submitted applications requesting the review of afatinib for patients with EGFR mutation-positive advanced NSCLC to regulatory authorities in a number of countries and regions worldwide, including the U.S., E.U. and Asia.
Afatinib is not approved by the FDA; its safety and efficacy have not been established.
Nintedanib (BIBF 1120) is an investigational orally-administered triple angiokinase inhibitor that targets three of the receptor tyrosine kinases shown to aid in the regulation of angiogenesis: fibroblast growth factor (FGF) receptor, platelet-derived growth factor (PDGF) receptor, and vascular endothelial growth factor (VEGF) receptor.
Nintedanib is being evaluated in various solid tumors – including advanced NSCLC, ovarian cancer, liver cancer (hepatic cell carcinoma), kidney cancer (renal cell carcinoma) and colorectal cancer. The advanced NSCLC and ovarian cancer clinical trials are in Phase III development. Nintedanib is also being investigated in Phase III trials for the treatment of Idiopathic Pulmonary Fibrosis (IPF), a progressive and severely debilitating lung disease.
Nintedanib is not approved by the FDA; its safety and efficacy have not been established.
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.
For information about participating in a Boehringer Ingelheim clinical trial, please visit www.bicancertrials.com or call 1.866.725.7110. Healthcare providers interested in learning more about Boehringer Ingelheim clinical trials in oncology can visit www.inoncologyus.com for additional information.
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 140 affiliates and more than 46,000 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.
As a central element of its culture, Boehringer Ingelheim has a demonstrated commitment to corporate social responsibility. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
In 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.
For more information please visit www.us.boehringer-ingelheim.com.
*Afatinib and nintedanib are investigational compounds; their safety and efficacy have not been established.
 Wu, Y., MD. LUX-Lung 6: A randomized, open-label, Phase III study of afatinib (A) vs gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung. Poster discusison (Abstract #8016) at American Society of Clinical Oncology, Chicago, June 2, 2013.
 Hanna, N., MD. LUME-Lung 2: A multicenter, randomized, double-blind, phase 3 study of nintedanib plus pemetrexed vs placebo plus pemetrexed in patients with advanced non-squamous non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy. Poster discussion (Abstract #8034) at American Society of Clinical Oncology, Chicago, June 2, 2013.
 Food and Drug Administration. Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. May 2007. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071590.pdf
 National Center for Biotechnology Information (NCBI). Reporting disease control rates or clinical benefit rates in early clinical trials of anticancer agents: useful endpoint or hype? December 2010. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21268434
 Geater, S.L., MD. LUX-Lung 6: Patient reported outcomes (PROs) from a randomized open-label, Phase III study in 1st-line advanced NSCLC patients (pts) harboring epidermal growth factor receptor (EGFR) mutations. Poster (Abstract #8061) at American Society of Clinical Oncology, Chicago, June 1, 2013.
 European Organisation for Research and Treatment of Cancer (EORTC). Glossary. Available at: http://groups.eortc.be/qol/glossary. Last accessed May 9, 2013.
 Mayo Clinic. Elevated Liver Enzymes. Available at: http://www.mayoclinic.com/health/elevated-liver-enzymes/MY00508. Last accessed April 23, 2013.
 American Cancer Society. Cancer Facts and Figures: 2012. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf. Last accessed April 27, 2012.
 Quest Diagnostics. Lung Cancer Mutation Panel (EGFR, KRAS, ALK). Available at: http://questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=Lung/TS_LungCancerMutation_Panel.htm . Last accessed May 18, 2012.
 Yu, J. et al. "Mutation-specific antibodies for the detection of EGFR mutations in non-small-cell lung cancer." Clinical Cancer Research; May 1, 2009. Available at: http://clincancerres.aacrjournals.org/content/15/9/3023.long. Accessed May 8, 2012
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