The LUX-Lung 1 trial compared afatinib to placebo in patients with advanced non-small cell lung cancer (NSCLC) whose disease progressed after receiving chemotherapy and a first-generation EGFR tyrosine kinase-inhibitor (TKI), gefitinib or erlotinib. The sub-group included in the analysis to be presented comprises two-thirds of all patients from the study (391/585) who were most likely to have EGFR mutations as determined by clinical criteria based on their response to and duration of prior treatment with EGFR-TKIs.

The results presented are an update of the initial results from the LUX-Lung 1 clinical trial, which were presented at the recent European Society for Medical Oncology (ESMO) meeting in Milan (2).

"We continue to be encouraged by the findings of this study as we move towards personalised treatments" said Vincent A. Miller, M.D. Principal Investigator, Medical Oncologist, Memorial Sloan-Kettering Cancer Center, USA. "These data not only demonstrate the activity of afatinib, but they suggest that a certain sub-group of patients - those most likely to have EGFR mutations - may respond more positively with afatinib."

Afatinib is an investigational orally-administered irreversible inhibitor of both the EGFR and human epidermal receptor 2 (HER2) tyrosine kinases that is under development in several solid tumors including NSCLC, breast and head and neck cancer.

As part of Boehringer Ingelheim's comprehensive LUX clinical trial programme, a phase III trial called LUX-Lung 3 has been started which will specifically investigate afatinib as a first-line treatment in patients with advanced NSCLC who harbour EGFR mutations.

About the LUX-Lung 1 trial
The LUX-Lung 1 trial (phase II b/III) compared afatinib to placebo in over 585 patients with advanced non-small cell lung cancer (NSCLC) whose disease has progressed after receiving both chemotherapy and a first-generation epidermal growth factor receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (gefitinib or erlotinib)

• Even though the LUX-Lung 1 trial did not meet the primary endpoint of prolonging overall survival 1 in the overall patient population, updated results from a post hoc analysis are to be presented for one large sub-group of patients who were likely to have EGFR mutations based on clinical criteria (391 patients). This showed:
  • A trend towards a prolonged overall survival for patients treated with afatinib, specifically an 11% improvement in survival probability (Hazard Ratio HR=0.9; 95% confidence interval of 0.69 to 1.18) (2). The Hazard Ratio of 0.9 indicates that there is an 11% reduction in the risk to die in the afatinib arm compared to the placebo arm. Updated, more mature survival results will be presented soon.
  • A significant four-fold improvement in progression-free survival (4.4 months vs 1 month for placebo). (2)
• The results for the overall population (irrespective of EGFR mutation status), showed:
  • There was a significantly higher rate of tumour control or shrinkage in those patients who took afatinib (disease control rate: 58%) versus those taking placebo (disease control rate: 19%); independently verified.
  • Afatinib significantly improved the lung-cancer related symptoms cough, dyspnea (shortness of breath) and pain, and delayed the time to deterioration of cough, individual dyspnea items and chest pain significantly.

Furthermore, the trial did not show any new or unexpected safety findings; the main side effects for afatinib were diarrhea and rash/acne. These side effects were usually well-managed by supportive care and dose reduction.

About Afatinib’s clinical trial programme: LUX Trial Programme
The LUX-trial programme is a comprehensive and robust programme that comprises more than ten trials conducted across the globe, investigating afatinib in a variety of different solid tumour types, including NSCLC, breast and head and neck cancer.

The LUX-Lung 1 trial was intended to investigate afatinib as a last-line treatment option, as only very few patients receive active therapies beyond third-line in advanced NSCLC. Surprisingly, more than two-thirds of the patients received additional therapy, which, despite a substantial improvement in progression-free survival, may have confounded the overall survival results.

LUX-Lung 2 is a phase II trial evaluating afatinib in NSCLC patients with EGFR mutations, either chemotherapy naïve or after one line of chemotherapy.

In two further ongoing global phase III trials, LUX-Lung 3 and LUX-Lung 6, the efficacy and safety profile of afatinib is compared to standard chemotherapy for first-line treatment of NSCLC patients with EGFR mutations in different geographical regions.

Another trial, LUX-Lung 5, is a global phase III trial in patients previously treated with erlotinib or gefitinib. This is the first randomised phase III trial investigating whether patients who initially benefit from treatment with afatinib alone may further benefit from afatinib beyond progression when given in combination with chemotherapy.

About Lung Cancer
Lung cancer is the most common and most deadly form of cancer in the world, accounting for 1.6 million new cancer cases annually and 1.4 million deaths (3) from lung cancer. Lung cancer remains an area of high unmet need, especially in its advanced stages where it is particularly aggressive and patients have limited treatment options. No approved therapy is currently available for patients with advanced lung cancer who have failed chemotherapy and progressed after treatments with EGFR TKI.

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 is committed to discovering and developing novel cancer treatments. This commitment is underpinned by using advances in science to develop a range of targeted therapies in areas of medical need, including 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. Afatinib is currently in phase III clinical development in NSCLC. In addition, the LUME-Lung phase III clinical trial programme, which is investigating BIBF 1120 in combination with standard second-line chemotherapy treatments for patients with advanced NSCLC, is ongoing. In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing inhibitors of polo-like kinase 1 (Plk1), a protein that is involved in the processes of cell division. These molecules are in the earlier stages of clinical development.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending 21% of net sales in its largest business segment Prescription Medicines on research and development.

For more information please visit www.boehringer-ingelheim.com.

1. Miller et al. Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2 + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1–2 lines of chemotherapy and erlotinib or gefitinib (LUX-Lung 1). Oral presentation at The European Society of Medical Oncology (ESMO) annual meeting, Milan, October 2010. Abstract ID: LBA1
2. Miller et al. Subgroup analysis of LUX-Lung 1: A randomized Phase III Trial of Afatinib (BIBW 2992) + Best Supportive Care (BSC) versus Placebo + BSC in Patients with NSCLC Failing 1-2 Lines of Chemotherapy and Erlotinib or Gefitinib. Oral presentation at Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, USA, 10 December, 2010
3. Cancer Research UK. CancerStats Key Facts on Lung Cancer and Smoking. Available at http://info.cancerresearchuk.org/cancerstats/types/lung/. Last accessed 30 September 2010.

* Afatinib (BIBW 2992) is an investigational compound - its safety and efficacy have not been fully established.