Head-to-head Phase III trial demonstrates superior progression-free survival for afatinib compared to erlotinib in patients with advanced squamous cell carcinoma of the lung

Ingelheim, Germany, 27 September 2014 – Phase III data from Boehringer Ingelheim’s LUX-Lung 8 trial, the first study to directly compare the efficacy of two different targeted agents in patients with advanced squamous cell carcinoma (SCC) of the lung, demonstrated superior progression-free survival (PFS: length of time before the tumour starts to progress) of afatinib compared to erlotinib.¹ Afatinib, an irreversible ErbB Family Blocker, showed significant improvement across several measures of efficacy, in particular for the primary endpoint of PFS compared to erlotinib in patients after failure of first-line chemotherapy.¹ Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, with SCC representing approximately 30% of NSCLC cases.^2,3 The results (abstract #1222O) are being presented today at the European Society for Medical Oncology (ESMO) 2014 Congress (September 26-30).

LUX-Lung 8 demonstrated that afatinib significantly reduced the risk of disease progression by 18% when compared to erlotinib, and delayed tumour growth (PFS by independent review: 2.4 vs. 1.9 months).¹ In addition, afatinib showed an improvement in the secondary endpoint of disease control rate (DCR: the percentage of patients who achieved complete response, partial response or stable disease, 46% vs. 37%). The objective response rate (ORR: the percentage of patients who achieved a partial or complete response to therapy) was numerically higher with afatinib compared to erlotinib (5% vs. 3%).¹

Favourable trends were noted in delaying the worsening of lung cancer symptoms and global health status/quality of life. The proportion of patients reporting improvement in cough and global health status/quality of life, respectively, was significantly higher with afatinib versus erlotinib.¹ Results of overall survival (OS: length of time patients live for), the key secondary endpoint, are not yet mature, and will therefore be assessed at a later stage in the trial and reported at a future medical congress.

Co-lead investigator Glen D. Goss, M.D., Director of Clinical and Translational Research, The Ottawa Hospital Cancer Center, University of Ottawa, Canada, commented: "The results of LUX-Lung 8 demonstrate the progression-free survival benefit for afatinib over erlotinib in advanced squamous cell carcinoma of the lung, a disease with poor prognosis for which there are currently limited treatment options."

Co-lead investigator Professor Jean Charles Soria, Head Drug Development Department, Gustave Roussy Cancer Centre, Paris, France, added: "Further, the treatment also resulted in a favourable impact on patients’ overall health and quality of life, an important consideration for physicians treating patients with such advanced lung cancer. We are awaiting with interest the results of the overall survival data."

The overall rate of severe (≥ grade 3) and serious adverse events was comparable between both therapies. Incidence of severe adverse events was 50.2% in patients treated with afatinib compared to 49.1% with erlotinib. A higher incidence of ≥ grade 3 diarrhoea and stomatitis were observed in patients treated with afatinib compared to erlotinib (≥ grade 3 diarrhoea: 9% vs. 2%; stomatitis: 3% vs. 0%), while there was a higher incidence of ≥ grade 3 rash/acne observed with erlotinib compared to afatinib (9% vs. 6%).1 See abstract #1222O (A randomized, open-label, phase III trial of afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following first-line platinum-based chemotherapy: LUX-Lung 8 (LL8),  27.09.2014, 16.00 – 17:45, Madrid) for full details.

Afatinib’s mode of action differs from other EGFR TKIs such as erlotinib, which target EGFR (ErbB1) only, in that it provides sustained, selective and complete ErbB Family blockade. Afatinib’s novel mode of action may lead to a distinct therapeutic benefit.

Professor Gerd Stehle, Vice President, Medicine Therapeutic Area Oncology, Boehringer Ingelheim commented: "These data add to the growing body of clinical evidence supporting the efficacy and safety of afatinib in the treatment of distinct types of lung cancer. They demonstrate, for the first time, afatinib’s superiority compared to another targeted treatment in advanced squamous cell carcinoma of the lung. The results are an important step in advancing treatments for these patients."

LUX-Lung 8 is the largest prospective trial to compare EGFR-targeting compounds in patients with advanced SCC of the lung. LUX-Lung 7, a second head-to-head trial evaluating afatinib versus gefitinib as a first-line treatment in EGFR mutation-positive NSCLC patients, is currently ongoing.

About afatinib
 Afatinib Backgrounder

Afatinib approved and investigational indications
Afatinib (GIOTRIF^®/GILOTRIF^®) is indicated for the treatment of distinct types of EGFR mutation-positive NSCLC. In this indication, afatinib is approved in a number of markets, including the EU, Japan, Taiwan and Canada under the brand name GIOTRIF^® and in the U.S. under the brand name GILOTRIF^®. It is under regulatory review in other countries. Afatinib is not approved in other indications.

Approval of afatinib for the treatment of EGFR mutation-positive NSCLC was based on the primary endpoint of progression-free survival from the LUX-Lung clinical trial programme where afatinib significantly delayed tumour growth when compared to standard chemotherapy.  In addition, data from the LUX-Lung 3 and 6 trials demonstrated that afatinib is the first treatment to show an overall survival benefit for patients with specific types of EGFR mutation-positive NSCLC compared to chemotherapy. A significant overall survival benefit was demonstrated in both trials individually for patients with the most common EGFR mutation (exon 19 deletions; del19) compared to chemotherapy.

Phase III trials of afatinib in squamous cell head and neck cancer and trials in other tumour types are ongoing. The results of the LUX-Head & Neck 1 trial will be presented at ESMO.

About Boehringer Ingelheim in Oncology
 Boehringer Ingelheim in Oncology Backgrounder

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

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