The FINANCIAL — GlaxoSmithKline’s (GSK) oral targeted agent Tyverb (lapatinib) demonstrated single agent activity and improvement in clinical response to the subsequent standard chemoradiation compared to placebo in a Phase II study of advanced squamous cell carcinoma of the head and neck (SCCHN). [1]
"These encouraging results, presented during the 33rd Congress of the European Society for Medical Oncology (ESMO), represent an important step in the development of lapatinib for head and neck cancer. Lapatinib is already being investigated further for head and neck cancer; an innovative Phase III adjuvant study (MAINTYNANCE) is currently recruiting across the world." GlaxoSmithKline reports.
Lapatinib is the first oral, small molecule, dual targeted therapy that works intracellularly (from inside the cell) to inhibit both EGFR and ErbB2 (HER2), two receptor proteins which are involved in tumour growth. [2] EGFR expression has been demonstrated to occur with high frequency in the majority of cancers including head and neck, ovarian, bladder and lung [3] and typically presents a more aggressive clinical course of the cancer. [4]
“These results show that the use of a dual tyrosine-kinase inhibitor like lapatinib may be clinically relevant not just in breast cancer, but maybe in other tumours such as head and neck cancer where EGFR is overexpressed,” said Paolo Paoletti, M.D., Senior Vice President, Oncology Research and Development, GSK. “We are committed to developing lapatinib in head and neck cancer through our global Phase III trial, which is extremely exciting and aims to set a new standard of care and improve patient survival. The trial is the largest ever conducted in the resectable locally advanced setting. It is currently open and enrolling.”
“The Phase II study results demonstrated clear clinical activity with monotherapy lapatinib in patients with squamous cell carcinoma of the head and neck,” said Josep Maria Del Campo, M.D., Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain, and primary investigator of the study. “Interestingly, it was also observed that treatment with lapatinib appeared to improve response to chemoradiation.”
In the Phase II study, 107 therapy-naïve patients with locally advanced SCCHN were randomised (2:1) to receive 1500 mg of oral lapatinib or placebo. Patients were treated with lapatinib for a duration of two to six weeks, after which all patients received standard treatment with concurrent platinum-based chemotherapy and radiation therapy. Patients were followed-up for 12 weeks after completion of chemoradiation. Tumour biopsies were taken at time of study enrolment (Day 0) and after two weeks of study participation (Day 14) for biomarker analysis.
During the short duration (14 days) of lapatinib treatment there was a modest, but statistically significant reduction in mean tumour cell proliferation in patients who had received lapatinib compared to the placebo arm (-8% vs. -2.7% respectively, p=0.039). In addition, a trend towards inducing death of cancer cells was observed in some patients.
In a subset of 40 patients who had radiological scans following a short duration of lapatinib monotherapy (approximately one month), four patients (17%, n=24) had a complete or partial response, compared with no responders on the placebo arm (n=16).
88 patients were determined to be evaluable for radiological analysis following their complete course of chemoradiation, i.e., they had radiology scans at baseline (enrolment) and post-chemoradiation (~weeks 8-12 after treatment). The results showed an improvement in response rate (complete response and partial response) for patients who had received lapatinib compared to the placebo arm (86 vs. 63% respectively. A difference in complete response rate between the two groups after they received chemoradiation was also observed; 28% of patients in the lapatinib arm achieved complete response compared to 7% of patients in the placebo arm;1suggesting lapatinib may enhance the effect of subsequent chemoradiation. The most common adverse events (AEs) observed after lapatinib followed by chemoradiation treatment included mucositis (70%), asthenia (58%), odynophagia (33%), dysphagia (30%), rash (10%), nausea (29%) vomiting (25%) and diarrhoea (4%) compared to 67%, 47%, 36%, 33%, 14%, 22%, 36% and 6% for the placebo arm respectively.
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