GlaxoSmithKline announced the start of an international phase III trial of its investigational cancer treatment Tykerb (lapatinib) in squamous cell carcinoma of the head and neck (SCCHN). This announcement follows the International Meeting on Innovative Approaches in Head & Neck Oncology, Barcelona, Spain, 22nd-24th February supported by the European Society for Therapeutic Radiology and Oncology (ESTRO), where GSK presented results from a phase I study of lapatinib in SCCHN.

This large adjuvant trial will compare the effectiveness of oral lapatinib versus placebo given in high-risk patients following surgery. SCCHN is the sixth most common cancer worldwide: 600,000 people are diagnosed with SCCHN annually1, 100,800 in Europe alone and 40,000 people die from the disease every year.

The design of this phase III trial was based on recent results from two large-scale, independent randomized studies that demonstrated the new standard of care in the post-operative treatment of high-risk SCCHN patients with additional use of chemotherapy. However, research suggests that approximately one quarter to one third of advanced head and neck cancers that are primarily treated with surgery and radiation therapy come back following treatment.

"The initiation of this trial represents another exciting step towards understanding the role of lapatinib in other tumour types beyond breast cancer," says Professor Jean Bourhis, Head of Radiation-Oncology Department, Institute Gustave Roussy, France and principal investigator for this trial. "There is a significant group of patients who are at high-risk of disease recurrence following surgery, and they need new treatments that can be combined with standard chemoradiation therapy."

This global, Phase III study will enrol 680 high-risk patients with locally advanced head and neck cancer (stages II, III and IVa) that have undergone surgery. Patients will receive, within four to seven weeks after surgery, either lapatinib (1500 mg) or placebo tablets once-daily with radiotherapy and cisplatin for seven weeks. After this time, patients will continue with either lapatinib or placebo treatment for one year. The principal objective will be to investigate the length of time without disease symptoms, and overall survival with other clinical factors will also be measured. Side effects will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

Results from a phase I dose-escalation study of lapatinib (doses ranged from 500 mg to 1500 mg) plus chemoradiation in 31 head and neck cancer patients were presented at the conference. Results identified 1500 mg of lapatinib taken once-daily with chemotherapy and radiotherapy as the optimal dose for this combination, and this dose was selected for the Phase III study. Additionally, 89% of patients had a tumour response to this combination treatment. The most common side effects in the Phase I study were mouth ulcers (87%), radiation skin injury (65%), nausea (61%), swallowing difficulties (52%) and vomiting (52%).

"Having already shown promise as a breast cancer treatment, we are very excited to continue investigating lapatinib in SCCHN," said Paolo Paoletti, MD, Senior Vice President, Oncology Medicine Development Centre, GSK. "Lapatinib may represent a new treatment approach to difficult-to-treat tumour types, such as head and neck cancer, offering hope to patients in need of a further treatment option."

Lapatinib blocks the activation of two key receptors, EGFR (ErbB1) and HER2 (ErbB2), associated with increased growth and development of this type of head and neck tumour. Stimulation of these receptors is associated with multiple processes involved in tumour growth. An excessive presence of these receptors has been reported in a variety of human tumours and is associated with poor outcome and reduced survival.

SCCHN is the most common form of cancer of the head and neck, and approximately two-thirds of all patients are diagnosed with advanced disease. EGFR and HER2 are two types of receptors found on tumours which play a key role in the development of this type of head and neck cancer. Researchers have found that the excessive expression of EGFR receptors is nearly universal in SCCHN disease, with large numbers of HER2 receptors present in 20 to 40 percent of tumours.

Lapatinib was discovered and developed by GSK as an oral once daily therapy, and is currently being investigated in breast cancer and other solid tumours. Lapatinib has proven efficacy in advanced breast cancer. Phase III results of lapatinib plus capecitabine show superior efficacy to capecitabine alone in women with HER2 positive advanced breast cancer who have progressed following prior therapy, including trastuzumab.

The most frequent side-effects related to lapatinib from clinical trials to date are mild to moderate (grade 1 or 2) diarrhoea, nausea, vomiting, fatigue and rash.

GSK is using advanced technologies, including pharmacogenomics, to better define patient populations that may respond to lapatinib.

Lapatinib is an investigational drug that is not yet approved for marketing by any regulatory body.

Lapatinib in combination with capecitabine has been submitted for marketing approval in the United States, European Union and Switzerland for the treatment of advanced or metastatic HER2 positive breast cancer in women who have progressed despite prior therapy, including trastuzumab. Registration dossiers have also been filed in Australia, Canada and New Zealand.