Value through Innovation25 October 2014
28 September 2012

Unprecedented progression-free survival benefit with afatinib* associated with clinically meaningful improvements in life-limiting lung cancer symptoms and better quality of life

New data from the LUX-Lung 3 trial in first-line patients with EGFR mutation positive NSCLC, presented at the ESMO 2012 Congress (European Society for Medical Oncology) shows that patients benefit from substantial improvements in lung cancer-related symptoms and have better quality of life when treated with the irreversible ErbB Family Blocker afatinib*.


Poster: #1229PD
Presentation: Sunday, September 30; 12:45 – 2:45 PM CEST
Poster Discussion Session: NSCLC, metastatic

Vienna, Austria, 28 September 2012 – Data from LUX-Lung 3, the largest and most robust registration trial to date** in patients with EGFR (ErbB1) mutation positive non-small cell lung cancer (NSCLC) shows that the novel compound afatinib*, an irreversible ErbB Family Blocker, leads to better and longer control and improvement of the most common lung cancer-related symptoms and better quality of life (QoL) compared to chemotherapy (pemetrexed and cisplatin), considered best-in-class for non-squamous (NSCLC).1,2 These findings further reinforce the outstanding first-line efficacy of afatinib* in patients with EGFR mutation positive NSCLC.

Analyses of patients' questionnaires for three pre-specified lung cancer symptoms (cough, dyspnoea and pain) showed that more afatinib*-treated patients experienced significant improvements in dyspnoea (64% vs. 50%; p=0.0103), a statistical trend towards improvement in pain (59% vs. 48%; p=0.0513) and numerical improvements in cough (67% vs. 60%; p=0.2444) compared to those treated with pemetrexed / cisplatin.1 Afatinib* also significantly delayed the time to deterioration for cough (HR=0.60; p=0.007) and dyspnoea (HR=0.68; p=0.0145) versus chemotherapy.1 Importantly, afatinib* treatment led to improved physical, role and cognitive functioning, and overall better QoL.1

"Lung cancer-related symptoms like fatigue, shortness of breath and pain are very distressing and have a dramatic impact on patients' quality of life.= said Dr Matthew Peters, chair of The Global Lung Cancer Coalition. “With around 90% of advanced NSCLC patients experiencing two or more disease-related symptoms and high levels of associated psychological distress3 it is important that we consider these endpoints when assessing the benefits of a treatment."

Previously presented LUX-Lung 3 trial data has shown that patients taking afatinib* as a first-line treatment lived for almost one year without their tumour growing again (median progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those treated with pemetrexed / cisplatin.Furthermore, NSCLC patients with tumours harbouring the two most common EGFR mutations taking afatinib* lived for well over a year without tumour progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.4 Patients with common EGFR mutations who experienced a greater PFS benefit also experienced a greater benefit in health-related QoL, symptom control and symptom improvement.1

Dr Vera Hirsh, Associate Professor, McGill University, Department of Medical Oncology, Royal Victoria Hospital, Montreal, Canada

Dr Vera Hirsh, Associate Professor, McGill University, Department of Medical Oncology, Royal Victoria Hospital, Montreal, Canada

"Following encouraging data presented earlier this year, the new data demonstrate that the positive progression-free survival outcomes with afatinib* also translate into additional benefits for patients in terms of quality of life and control and improvement of symptoms,” commented Dr Vera Hirsh, Associate Professor, McGill University, Department of Medical Oncology, Royal Victoria Hospital, Montreal, Canada. "This further supports the potential of this treatment option in first-line treatment of metastatic NSCLC to effectively help those patients harboring EGFR mutations."

Afatinib* is an irreversible ErbB Family Blocker, thus it differs from currently available targeted therapies in that it irreversibly and completely inhibits ErbB receptor signal transduction, blocking the key pathways that help tumour cells grow, migrate and metabolise.5 This novel mode of action may lead to a distinct therapeutic benefit and has provided the basis for initiation of the LUX-Lung trial programme.5

This years' ESMO 2012 Congress sees the presentation of 13 abstracts assessing the efficacy and safety of Boehringer Ingelheim's investigational oncology compounds afatinib* and nintedanib*.

Presentations of Boehringer Ingelheim Investigational Oncology Compounds at ESMO 2012 Congress

Title First Author Details
Afatinib*
LUX-Lung 3: Activity of afatinib in uncommon epidermal growth factor receptor (EGFR) mutations in LUX-Lung 3, a phase III trial of afatinib or cisplatin/pemetrexed in EGFR mutation-positive lung cancer J.C.-H. Yang 1252P
Date: Saturday, 29 September
Time: 13:00 – 14:00 PM CEST
Phase II trial of afatinib as a third-line treatment for Korean patients (pts) with wild-type epidermal growth factor receptor (wtEGFR) stage IIIB/IV lung adenocarcinoma M.-J.A. Ahn 1292P
Date: Saturday, 29 September
Time: 13:00 – 14:00 PM CEST
LUX-Lung 3: Symptom and health-related quality of life results from a randomized phase III study in 1st-line advanced NSCLC patients harbouring EGFR mutations L.V. Sequist 1229PD
Date: Sunday, 30 September
Time: 12:45 – 14:45 PM CEST
A Phase I study of daily afatinib, an irreversible ErbB Family Blocker, combined with weekly paclitaxel and 2-weekly bevacizumab in patients with advanced solid tumours D. Enting 464P
Date: Monday, 1 October
Time: 13:00 – 14:00 PM CEST
Phase I study to compare safety and pharmacokinetics of afatinib, an oral irreversible ErbB Family Blocker, in non-cancer subjects with hepatic impairment to matched healthy subjects D. Schnell 468P
Date: Monday, 1 October
Time: 13:00 – 14:00 PM CEST
Phase I safety and tolerability of once daily oral afatinib (A) (BIBW 2992) in combination with gemcitabine (G) in patients (pts) with advanced solid tumours S. Zanetta 478P
Date: Monday, 1 October
Time: 13:00 – 14:00 PM CEST
Phase I safety and tolerability of once daily oral afatinib (A) in combination with docetaxel (D) in patients (pts) with relapsed or refractory advanced solid tumours H. Senellart 494P
Date: Monday, 1 October
Time: 13:00 – 14:00 PM CEST
LUX-Lung 8: A randomized, open-label, Phase III trial of afatinib vs. erlotinib in patients with advanced squamous cell carcinoma of the lung as second-line therapy following first-line platinum-based chemotherapy G. Goss 509TiP
Date: Monday, 1 October
Time: 13:00 – 14:00 PM CEST
LUX-Lung 5: Impact of EGFR mutation status on clinical benefit from BIBW 2992 in patients (pts) with advanced non-small cell lung cancer (NSCLC) progressing after chemotherapy (ctx) and erlotinib (E) or gefitinib (G) – A single center experience J. Köhler 1339
Abstract Only
Activity of afatinib/cetuximab in patients (pts) with EGFR mutant non-small cell lung cancer (NSCLC) and acquired resistance (AR) to EGFR inhibitors Y.Y. Janjigian 1227O
Date: Sunday, 30 September
Time: 9:00 – 11:00 AM CEST
Combination Afatinib* and Nintedanib*
Phase I study of afatinib (BIBW 2992), an ErbB Family Blocker plus nintedanib (BIBF 1120), a triple angiokinase inhibitor, in patients (pts) with advanced solid tumours J.-C. Soria 446PD
Date: Sunday, 30 September
Time: 13:00 – 14:00 PM CEST
Nintedanib*    
Phase I study of nintedanib (BIBF 1120) in European patients with advanced hepatocellular carcinoma D. Palmer 740P
Date: Sunday, 30 September
Time: 13:00 – 14:00 PM CEST
Early data from a phase I study of nintedanib (BIBF 1120) in Asian patients with advanced hepatocellular carcinoma C.-J. Yen 744P
Date: Sunday, 30 September
Time: 13:00 – 14:00 PM CEST


Boehringer Ingelheim Media Briefing at ESMO 2012LUNG CANCER: what lies beneath the data
WHEN:
Saturday 29 September 2012, 17:30–19:00
WHERE: Industry Press Room, Level 1, Lounge 1, ESMO 2012 Congress Venue (Austria Center Vienna), Vienna, Austria

Highlights from the session, including the webcast will also be available on www.thewhiteroom.info from Monday 1 October. In the meantime, visit this online resource centre for further information.

Notes to Editors

About Afatinib*
Afatinib* is an irreversible ErbB Family Blocker which inhibits signal transduction of all kinase receptors from the ErbB Family,5 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 & neck cancer.
The European Medicines Agency (EMA) has recently accepted the submission of a Marketing Authorisation Application from Boehringer Ingelheim for approval of afatinib* as a treatment in patients with EGFR mutation positive NSCLC.

About LUX-Lung 3 Trial
LUX-Lung 3 is the largest and most robust registration trial to date in patients with advanced EGFR mutation positive lung cancer. LUX-Lung 3 is a global, randomized, open-label, Phase III trial and the first to directly compare a tyrosine kinase inhibitor (afatinib*) to the standard chemotherapy agents, pemetrexed and cisplatin. The study included 345 previously untreated patients with EGFR mutation positive NSCLC.4

The most common drug-related adverse events observed in the afatinib* treatment arm were diarrhoea (95%), rash/acne (89%), and mucositis/stomatitis (72%). 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 treatment due to diarrhoea.

About Lung Cancer
Lung cancer is the most common and most deadly form of cancer in the world.6 In Europe, it accounts for 391,000 new cancer cases annually, and 342,000 deaths each year.7 Overall, lung cancer is the cause of 19.9% of all cancer deaths in Europe.7 Thirteen percent of all new cases of cancer are lung cancers8 and smoking is attributed as the main cause.9

Early testing for tumour 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 tumours harbouring EGFR mutations, with approximately 90% of these accounting for two mutations (del19 or L858R).10

About Nintedanib*
Nintedanib* is a triple angiokinase inhibitor that blocks three growth factor receptors simultaneously: vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR alpha and beta) and fibroblast growth factor receptors (FGFR 1-3).11 All three receptors are crucially involved in the formation and maintenance of new blood vessels (angiogenesis); their blockade may lead to the inhibition of angiogenesis, which plays a critical role in tumour growth and spread.12,13

Nintedanib* is currently being investigated in patients with a number of various solid tumours including advanced non-small cell lung cancer (NSCLC), ovarian cancer, liver cancer (hepatic cell carcinoma), kidney cancer (renal cell carcinoma), and colorectal cancer.

About Boehringer Ingelheim in Oncology
Building on scientific expertise and research 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*, 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.

For more information please visit:www.boehringer-ingelheim.com, www.thewhiteroom.info and www.newshome.com.

References
1Abstract no: 1229PD. Sequist L. V. et al. LUX-Lung 3: Symptom and health-related quality of life results from a randomized phase III study in 1st-line advanced NSCLC patients harbouring EGFR mutations. ESMO 2012 Congress. Available at: http://abstracts.webges.com/myitinerary/session-148.html?congress=esmo2012#.UFdGtBr1LSY.gmai
2Scagliotti GV, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.J Clin Oncol 2008;26(21):3543–51
3Tanaka K. et al. Impact of Dyspnea, Pain, and Fatigue on Daily Life Activities in Ambulatory Patients with Advanced Lung Cancer. Journal of Pain and Symptom Management. Journal of Pain and Symptom Management 2002, Vol. 23 No. 5.
4Abstract no: LBA7500. Yang et al. 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.
5Solca, F. et al. Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (Fast Forward 10 August 2012) . J Pharmacol Exp Ther 2012 343 (2).
6Ferlay J et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127 2893-2917.
7Ferlay J et al. Estimates of cancer incidence and mortality in Europe in 2008. EJC 2010; 46 765-781.
8Cancer Research UK. UK lung cancer incidence. CancerStats – Key Facts 2009. [Online] Available at: http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/ [Last Accessed Sepember 2012].
9Allen J et al. J Natl Compr Canc Netw 2008;6(3): 285-293.
10Quest Diagnostics – Lung Cancer Mutation Panel. [Online] Available at: http://www.questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=TS_LungCancerMutation_Panel.htm [Last Accessed September 2012].
11Hilberg F et al. BIBF1120: Triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy. Cancer Research 2008;68(12): 4774-4782.
12Folkman N. Clinical Applications of Research on Angiogenesis. New England Journal of Medicine 1995;333: 1757-1763
13Ellis, L.M. and Hicklin, D.J. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nature Reviews Cancer 2008;8: 579-591.

*Afatinib is an investigational compound. Its safety and efficacy have not yet been fully established.
** LUX-Lung 3 included 345 patients in 133 sites in 25 countries. Results were independently reviewed. The chemotherapy arm was cisplatin / pemetrexed, considered the most efficacious platinum doublet chemotherapy in advanced and metastatic lung cancer.2 The trial prospectively selected EGFR (ErbB1) mutations, rather than retrospectively. The trial was the largest trial conducted in lung cancer patients with EGFR (ErbB1) mutations. The trial included patients from all over the world including Caucasians and Asians.

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