Afatinib* as first line efficacy in EGFR mutations lung CA !!

 Afatinib* delivers unprecedented first line efficacy in patients with EGFR mutation positive lung cancer in registration trial   June 4, 2012, 12:01 a.m. EDT LUX-Lung 3 results highlighted at the official ASCO Press Conference: Afatinib* delays cancer progression significantly more than the best standard chemotherapyINGELHEIM, Germany, Jun 04, 2012 (BUSINESS WIRE) -- For NON-US media only The LUX-Lung 3 Phase III results showed that lung cancer patients taking the novel compound afatinib*, an irreversible ErbB Family Blocker, as a first-line treatment, lived for almost one year before their tumour started to grow again (progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those on standard chemotherapy (pemetrexed / cisplatin).(1) Importantly, patients taking afatinib* with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) lived for well over a year without progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.(1) Boehringer Ingelheim's registration trial LUX-Lung 3 is investigating the company's front runner molecule afatinib*, and is the largest and most robust trial to date in EGFR (ErbB1) mutation positive advanced lung cancer patients. The primary endpoint was progression-free survival (PFS). "Not only did LUX-Lung 3 meet its primary endpoint, but it also showed that afatinib*, especially in patients with the most common EGFR mutations, almost doubled the progression free survival time compared to chemotherapy." commented Prof. James Chih-Hsin Yang, Director of the Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan and principal investigator of the LUX-Lung 3 trial. "Based on this proven efficacy in the largest and most robust registration trial, coupled with its novel mode of action, afatinib* may become one of the most valuable treatment options for this distinct patient population." The delay in disease progression for afatinib*-treated patients was associated with better control of life-restricting disease-related symptoms.(1) More patients taking afatinib* experienced improvement of symptoms such as dyspnea (shortness of breath), cough and chest pain. Afatinib* also delayed the onset of these symptoms.(1) A standard lung cancer questionnaire to assess the quality of life of cancer patients revealed that afatinib* treatment translates into significantly improved quality of life (e.g. at work and during household activities).(1) "We are pleased to see that the first compound from our large oncology portfolio has clearly demonstrated its clinical benefit and the potential to effectively help those lung cancer patients harboring EGFR mutations." said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The results of the LUX-Lung 3 clinical trial are very encouraging and we strive to bring this personalised treatment to patients in need as soon as possible." The most common adverse events associated with afatinib* treatment were diarrhea and skin-related side effects. These adverse events were as expected with EGFR inhibition, consistent with previous studies, and were predictable, manageable and reversible.(1) These rarely led to discontinuation of the treatment.(1) To further explore the potential of afatinib* as a lung cancer treatment, Boehringer Ingelheim has initiated two new trials aimed at comparing afatinib* head-to-head with targeted treatment agents. Both trials are currently recruiting patients. LUX-Lung 7 is a Phase IIb trial evaluating afatinib* versus gefitinib as a first-line treatment in EGFR mutation positive NSCLC patients. LUX-Lung 8 is a Phase III trial evaluating afatinib head-to-head versus erlotinib in second-line treatment of squamous cell carcinoma of the lung. Afatinib* is different to currently available targeted therapies in that it irreversibly blocks the ErbB Family of receptors, meaning afatinib* blocks EGFR (ErbB1) as well as the other relevant members of the ErbB Family, all of which can be involved in pathways that help tumour cells grow, migrate and metabolise. Investigation of the clinical relevance of afatinib*'s unique mode of action which could potentially lead to a greater effect on the tumour, has provided the basis for initiation of the LUX-Lung trial programme. Full data from the trial will be presented today in a late-breaking oral presentation at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

About LUX-Lung 3 Trial LUX-Lung 3 is a large, randomized, open-label, Phase III registration study comparing afatinib* to two chemotherapy agents, pemetrexed and cisplatin, as first-line treatment for patients with stage IIIb or IV NSCLC harboring an EGFR mutation. The study included 345 patients with EGFR mutation positive NSCLC globally. LUX-Lung 3 is the largest trial to date in patients with EGFR mutation positive NSCLC and the first study in this population to use pemetrexed / cisplatin as a comparator.(1) 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.

About Lung Cancer Lung cancer is the most common and most deadly form of cancer in the world: it accounts for 1.6 million new cancer cases annually. Because of its poor prognosis, 1.38 million deaths each year are attributable to lung cancer.(3) Overall, lung cancer is the cause of 18% of all cancer deaths.(3) Thirteen percent of all new cases of cancer are lung cancers(4)and smoking is attributed as the main cause.(5) Early testing for EGFR mutation status of lung cancer patients is critical in improving patient outcomes. Between 10-15% of Caucasian and 40% of Asian NSCLC patients have EGFR mutations, with 90% of these a result of two mutations (del19 or L858R).(2)

About Afatinib* Afatinib* is an irreversible ErbB Family Blocker which inhibits signal transduction of all kinase receptors from the ErbB Family(2), which is known to play a critical role in the growth and spread of the most pervasive cancers and cancers associated with high mortality (lung, breast, and head & neck cancers). Afatinib* is currently also in Phase III clinical development in breast cancer and head and neck cancer.

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 programme to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world's leading cancer centres, Boehringer Ingelheim's commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumours and haematological cancers. The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. Nintedanib* (BIBF 1120), an angiogenesis inhibitor is currently in Phase III clinical development in NSCLC and ovarian cancer. In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing an inhibitor of polo-like kinase 1 (Plk1), volasertib*, a protein that is involved in the processes of cell division. The compound is in Phase II development for acute myeloid leukaemia. Boehringer Ingelheim's oncology pipeline is evolving and demonstrates the company's continued commitment to advance the disease area.

Boehringer Ingelheim 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 endeavours. In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales. *Afatinib, nintedanib (BIBF 1120) and volasertib are investigational compounds. Their safety and efficacy have not yet been fully established.

References (1) Abstract no: LBA7500, 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 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2012. (2)Jang, T.W. et al. 2009. EGFR and KRAS Mutations in Patients With Adenocarcinoma of the Lung. The Korean Journal of Internal Medicine, March; 24(1), pp.48--54. (3)Ferlay J et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127 2893-2917. (4)Cancer Research UK. UK lung cancer incidence. CancerStats -- Key Facts 2009. [Online] Available at: http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/ [Last Accessed April 2009]. (5)Allen J et al. J Natl Compr Canc Netw 2008;6(3): 285-293.

SOURCE: Boehringer Ingelheim