Afatinib demonstrates significant progression-free survival of almost one year in EGFR mutation-positive advanced NSCLC

RIDGEFIELD, Conn., June 4, 2012 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that the company's pivotal Phase III clinical trial, LUX-Lung 3, investigating afatinib as a first-line treatment in patients with stage IIIb or IV non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, met its primary endpoint of progression-free survival (PFS). 

The study evaluated 345 patients with NSCLC across a variety of EGFR mutations.  Results showed that within the general study population, patients assigned to the afatinib arm lived for 11.1 months before their tumor started to grow again (PFS) versus 6.9 months for those patients in the chemotherapy arm (pemetrexed/cisplatin).  The hazard ratio was 0.58 (95% CI: 0.43-0.78) (p=0.0004).  Approximately 90 percent of patients in the study had the most common EGFR mutations (Del19 and L858R).  In this subset, patients in the afatinib arm lived for a median of 13.6 months before their tumor started to grow again, versus a median of 6.9 months for those patients in the chemotherapy arm.  The hazard ratio in this patient subset was 0.47 (95% CI: 0.34-0.65) (p<0.0001).[1]  Data were presented today in a late-breaking oral presentation at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"Data from LUX-Lung 3 show that in patients with EGFR genetic mutations, afatinib demonstrated a significant and clinically meaningful delay in the progression of NSCLC, compared with combination pemetrexed and cisplatin," said Berthold Greifenberg, MD, Vice President, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc.  "These results add to the growing body of evidence supporting EGFR testing as an opportunity to inform and personalize the treatment of patients with EGFR mutation-positive NSCLC.  This further underscores Boehringer Ingelheim's commitment to advancing the research and development of its compounds with the goal of improving the lives of patients with cancer."

The most common drug-related adverse events observed in the afatinib treatment arm were diarrhea (95%), rash (62%) and paronychia (57%).  The most common drug-related adverse events observed in the chemotherapy arm (pemetrexed /cisplatin) were nausea (66%), decreased appetite (53%) and vomiting (42%).  There was a low discontinuation rate associated with treatment-related adverse events in the trial (8% discontinuation rate for afatinib; 12% for chemotherapy).  One percent of patients in the afatinib arm discontinued due to diarrhea.[1]

"Now that we are testing more patients for specific subtypes of lung cancer, we realize that EGFR mutation-positive lung cancer is a big problem. There may be up to 38,000 Americans diagnosed with this disease each year," said Lecia V. Sequist, MD, MPH, Medical Oncologist at Massachusetts General Hospital Cancer Center, Assistant Professor of Medicine at Harvard Medical School, and one of the Principal Investigators for LUX-Lung 3.  "There is still a great need for additional treatment options, particularly in the United States, where there are currently no therapies approved specifically for use in EGFR mutation-positive lung cancer." 

About LUX-Lung 3

LUX-Lung 3 is a randomized, open-label, Phase III study comparing the investigational oral, once-daily therapy, afatinib, to a combination chemotherapy regimen as first-line treatment for patients with stage IIIb or IV NSCLC harboring an EGFR mutation.  The study randomly assigned 345 patients with EGFR mutation-positive NSCLC to receive afatinib (n=230) or pemetrexed/cisplatin (n=115).  LUX-Lung 3 is the largest Phase III trial to date in first-line EGFR mutation-positive, advanced, metastatic NSCLC patients, and the first to use pemetrexed/cisplatin as a comparator in this population.  The primary endpoint was PFS.  Secondary endpoints of LUX-Lung 3 included objective response, duration of responses, patient-reported outcomes (including quality of life), safety and overall survival.[1]  

About Lung Cancer

In the United States, lung cancer is the second most common cancer.  In 2012, an estimated 226,160 new cases of lung cancer will be diagnosed in the United States and an estimated 160,340 Americans will die from the disease.  NSCLC is the most common form of lung cancer, accounting for about 85 percent of all diagnoses.[2]  Between 10 and 15 percent of Caucasians and approximately 40 percent of Asians with NSCLC have EGFR mutations[3] – 90 percent of which are the result of two mutations (Del19 or L858R).[4]

About Afatinib

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 NSCLC, head and neck and breast cancer.  Afatinib is not approved by the FDA; its safety and efficacy have not been established.

About the Afatinib LUX-Lung Clinical Trial Program

The LUX-Lung clinical trial program is investigating the use of afatinib in various settings of advanced NSCLC, including in patients harboring EGFR mutations and those with recurrent disease.  These trials include:

• LUX-Lung 1, a Phase IIb/III trial investigating afatinib plus best supportive care (BSC) versus placebo plus BSC in NSCLC patients who were previously treated with first-line chemotherapy and the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib or gefitinib.
• LUX-Lung 2, a Phase II trial evaluating afatinib in NSCLC patients with EGFR mutations, either treatment-naive or after one line of treatment with chemotherapy.
• LUX-Lung 3, a Phase III trial investigating afatinib as a first-line treatment in patients with advanced NSCLC with EGFR mutations. 
• LUX-Lung 4, a Phase I/II trial investigating afatinib in NSCLC patients who have progressed after conventional EGFR-TKI treatment. 
• LUX-Lung 5, a Phase III trial investigating afatinib in patients with advanced or metastatic NSCLC previously treated with erlotinib or gefitinib.
• LUX-Lung 6, a Phase III trial investigating the efficacy and safety of afatinib compared to standard chemotherapy for first-line treatment of NSCLC patients with EGFR mutations.
• LUX-Lung 7, a Phase IIb trial evaluating afatinib head-to-head versus gefitinib as a first-line treatment in patients with advanced NSCLC with EGFR mutations. 
• LUX-Lung 8, a Phase III trial evaluating afatinib head-to-head versus erlotinib in second-line treatment of squamous cell carcinoma of the lung. 

For more information on these trials, please visit www.clinicaltrials.gov. 

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 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.  

If you or someone you know is interested in participating in a Boehringer Ingelheim clinical trial, please visit www.bicancertrials.com or call 1.866.725.7110.  If you are a healthcare provider and are interested in learning more about BI clinical trials in oncology, please 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 145 affiliates and more than 44,000 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 pledges to act socially responsible. 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.

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

References 

[1] Yang, James Chih-Hsin Yang, MD, PhD.  LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations.  Oral presentation at American Society of Clinical Oncology, Chicago, June 4, 2012.

[2] 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.

[3] 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.

[4] 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.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.