Boehringer Ingelheim's afatinib achieves primary endpoint in global Phase III study in recurrent/metastatic head and neck squamous cell cancer

Boehringer Ingelheim's afatinib achieves primary endpoint in global Phase III study in recurrent/metastatic head and neck squamous cell cancer

Results from the LUX-Head & Neck 1 study show afatinib significantly delayed tumour growth versus chemotherapy in patients following failure of their previous treatment, reducing the risk for disease progression by 20%1

Head and neck cancer has a very poor prognosis with no well-defined standard of care after failure of previous therapy2

Data are encouraging for the ongoing pivotal LUX-Head & Neck clinical trial programme investigating afatinib in different settings of head and neck squamous cell cancer

Ingelheim, Germany, 27 September 2014 – Boehringer Ingelheim today announced Phase III data from the LUX-Head & Neck 1 study evaluating the efficacy and safety of afatinib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell cancer (HNSCC) versus methotrexate (a chemotherapy). The results of this global trial, with 483 patients from 19 countries, showed that afatinib, a once-daily, irreversible ErbB blocker, is the first tyrosine kinase inhibitor (TKI) to significantly delay tumour growth versus chemotherapy in patients with head and neck squamous cell cancer after failure of previous therapy.1 Results of this late-breaking abstract (abstract #LBA29) will be presented today at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain (September 26-30).

LUX-Head & Neck 1 met its primary endpoint of progression-free survival (PFS: length of time before the tumour starts to progress) by showing that patients taking afatinib, after failure of previous platinum-based chemotherapy, experienced a significant delay in tumour growth of 2.6 months versus 1.7 months with chemotherapy. This translated into a 20% reduction in risk of disease progression.1 With regard to secondary endpoints, afatinib significantly improved the disease control rate (DCR: the percentage of patients whose tumour size was stable or reduced, 49.1% vs. 38.5%), and the objective response rate (ORR: percentage of patients who achieved a partial or complete response to therapy) was numerically higher with afatinib compared to chemotherapy (10.2% vs. 5.6%). No significant difference between afatinib and chemotherapy was observed regarding overall survival (median 6.8 vs. 6.0 months).1

In quality-of-life questionnaires, patients taking afatinib reported significantly less pain and a delay in time to worsening of symptoms including pain, swallowing and global health status (overall health and quality of life), when compared to chemotherapy.1

Professor Jan Vermorken, M.D., Department of Medical Oncology, Antwerp University Hospital, Belgium, commented: "Afatinib achieved the primary endpoint, in showing an improved progression-free survival in a global Phase III trial versus standard chemotherapy. In addition, there were some favourable patient reported outcomes with respect to pain, swallowing and global health status when compared to standard chemotherapy. These data provide additional insight into evaluating this agent in this difficult-to-treat disease."
The most frequent drug-related severe adverse events (> grade 3) were rash/acne (9.7%) and diarrhoea (9.4%) with afatinib, and leukopenia (15.6%) and stomatitis (8.1%) with chemotherapy. The most common side effects in patients treated with afatinib compared to chemotherapy were rash/acne (74.4% vs. 8.1%), diarrhoea (72.2% vs. 11.9%) and paronychia (nail infection) (14.4% vs. 0%), and with chemotherapy compared to afatinib were stomatitis (43.1% vs. 39.1%), fatigue (31.9% vs. 24.7%) and nausea (22.5% vs. 20.0%). There were fewer drug-related dose reductions and discontinuations for patients taking afatinib compared to chemotherapy.1 See abstract #LBA29 (Afatinib versus methotrexate as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: results of the randomised, open-label, phase III trial LUX-Head & Neck 1, 27.09.2014, 09:15 – 10:45, Bilbao) for full details.
Professor Gerd Stehle, Vice President, Medicine Therapeutic Area Oncology, Boehringer Ingelheim commented: "Boehringer Ingelheim is committed to helping patients with devastating diseases and to exploring new treatment options. We are pleased to be presenting these data which, further to the established efficacy of afatinib in distinct types of non-small cell lung cancer, now demonstrate the broadening clinical potential of afatinib. This is very encouraging for our ongoing LUX-Head & Neck clinical trial programme."

About LUX-Head & Neck 1 trial
In the randomised, open-label Phase III LUX-Head & Neck 1 trial, patients with R/M HNSCC after progression on/after platinum-based therapy were randomized 2:1 to 40 mg/day oral afatinib (n=322) or 40 mg/m2/week intravenous methotrexate (n=161).

About LUX-Head & Neck clinical trial programme
The LUX-Head & Neck clinical trial programme is evaluating patients in the second line R/M setting after first-line platinum based therapy and as adjuvant therapy in the loco-regionally advanced setting. These trials include:

LUX-Head & Neck 1 and 3 (Clinical Trial Identifier NCT01345682 and NCT01856478), Phase III trials that investigate afatinib in patients with R/M HNSCC who have progressed on/after platinum-based chemotherapy. Estimated study completion dates: July 2015 and April 2016 respectively.
LUX-Head & Neck 2 and 4 (Clinical Trial Identifier NCT01345669 and NCT02131155), Phase III trials that evaluate afatinib in patients with locally advanced head and neck cancer after chemo-radiotherapy. Estimated study completion dates: May 2019 and August 2020 respectively.
About head and neck cancer
Head and neck cancer is the term used to describe a wide range of malignant tumours originating in the airway and swallowing tract (e.g. lip, oral cavity, nose, sinuses, throat and voice box). Squamous cell carcinoma is the most common type comprising 90% of head and neck cancers.2 Patients with R/M HNSCC have a poor prognosis with no well-defined standard of care after first-line platinum-based therapy.2

About afatinib
http://www.newshome.com/oncology/lung-cancer/afatinib-backgrounder.asp

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 carcinoma of the lung (SCC) and trials in other tumour types are ongoing.

About Boehringer Ingelheim in Oncology
http://www.newshome.com/oncology/general-oncology/boehringer-ingelheim-oncology-research-and-development.aspx

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.

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

1 Machiels JPH, Haddad RI, Fayette J., et al. Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: primary efficacy results of LUX-Head & Neck 1, a phase III trial. Abstract #LBA29 presented at the European Society for Medical Oncology (ESMO) 2014 Congress, Madrid, Spain. 26 – 30 September 2014.
2 Ferrarotto R. and Gold K A. Afatinib in the treatment of head and neck squamous cell carcinoma. Expert Opinion. 2014. 23 (1). 135 – 143.

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