Promising Combination Of Targeted Cancer Medicines Provides Greater Hope For Future Treatment Of Lung Cancer
New preliminary results from a Phase II study presented at the European Society for Medical Oncology (ESMO) congress show that a new investigational compound, MetMAb, in combination with erlotinib nearly doubled the time that certain non-small cell lung cancer (NSCLC) patients lived without their disease getting worse compared to placebo plus erlotinib.1
MetMAb – a monovalent, one-armed antibody – plus erlotinib raised median PFS to 12.4 weeks in patients whose tumours were high MET (where high levels of the MET expression receptor are present) compared to 6.4 weeks with placebo plus erlotinib (HR=0.56, p=0.05).1 Interestingly, 54% of the patients enrolled in the study had high MET expressing tumours so the potential benefits of this combination treatment would be significant.1 An overall survival (OS) benefit was also observed in MET-high NSCLC patients on MetMAb plus erlotinib compared to MET-high patients on placebo plus erlotinib (HR 0.55, p=0.11).
“Lung cancer is a very difficult disease to treat and any new treatment options are therefore always welcome,” said Professor Ken O’Byrne, Consultant Oncologist, St James’s Hospital, Dublin. “This study was conducted amongst a group of patients who had already been treated with standard chemotherapy regimens, so to see such improvements in PFS in a substantial proportion of the NSCLC patient population is quite remarkable. We look forward to seeing the full results of this trial and ongoing research into MetMAb with erlotinib as this combination may well provide an important future treatment option for clinicians and patients alike.”
MET, which is the target for MetMAb, is a signaling receptor on the cell surface that appears to play a pivotal role in controlling the growth of some types of cancer. If abnormally activated, MET has been associated with a worse prognosis in NSCLC and has also been implicated in resistance to EGFR inhibition in EGFR-mutated NSCLC.1 Consequently, targeting dual inhibition of MET/EGFR may result in positive treatment outcomes for NSCLC.
Most adverse events seen in this study were those associated with erlotinib, mainly rash and diarrhoea.1 MetMAb is not currently licensed in the UK.
MetMAb is a monoclonal monovalent antibody (one-armed antibody) that binds specifically to the cell surface MET receptor, blocking hepatocyte growth factor (HGF)-mediated activation. MET can be inappropriately activated in many cancers such as lung, metastatic breast, kidney and gastric by different mechanisms, such as over expression and a variety of mutations, which lead to invasive cancer growth.
Abnormal MET activation has been associated with worse prognosis in non-small cell lung cancer (NSCLC), and has been implicated in resistance to Epidermal Growth Factor Receptor (EGFR) inhibition in EGFR-mutated NSCLC. The predominant mechanism by which MET becomes activated is through binding of its ligand, HGF. MetMAb binds specifically to MET, blocking HGF-mediated activation. This novel approach of dual inhibition of MET/EGFR could provide promising treatment options for NSCLC.
About the Phase II study1
The Phase II study (OAM4558g) is a global randomised, double-blind study comparing MetMAb (15mg/kg IV q3wks) plus erlotinib (ME) to placebo plus erlotinib (PE) in 2nd/3rd line NSCLC. 128 patients were randomised from 3/2009 to 3/2010 to ME (n=64) or PE (n=64). Eligible patients on the PE arm were allowed to crossover to ME following progression. Patients were stratified by histology, ECOG PS and smoking status. Archival tissue was mandatory for determination of MET expression by IHC. Co-primary endpoints of the study were PFS in the MET-high and overall populations. Secondary endpoints include overall survival and safety. Most adverse events seen in this study were those already associated with erlotinib, mainly rash and diarrhoea. With the exception of oedema (fluid retention) overall toxicity for MetMAb in combination with Tarceva was comparable to Tarceva alone. MET-low NSCLC patients had worse PFS when treated with MetMAb plus erlotinib as compared to placebo plus erlotinib (HR 2.01, p=0.04). MET-low NSCLC patients had worse overall survival when treated with MetMAb plus erlotinib as compared to placebo plus erlotinib (HR 3.26, p=0.01). An overall survival (OS) benefit was also observed in MET-high NSCLC patients on MetMAb plus erlotinib compared to MET-high patients on placebo plus erlotinib (HR 0.55, p=0.11).
About Lung Cancer
Lung cancer is Britain’s biggest cancer killer with over 39,000 new cases diagnosed each year.2 Of these patients, only 20% will survive a year3 and only 8% will survive five years.4 Lung cancer kills 3,000 more women every year than breast cancer and accounts for more male cancer deaths than prostate, pancreatic, kidney and stomach cancer combined.5 NSCLC accounts for approximately 80% of lung cancer cases in the UK.6 Despite being the UK’s biggest cancer killer, lung cancer receives less than 4% of government research funding, compared to around 20% for breast, 12% for colorectal and 8% for prostate cancer.7
1. Global Press Release
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5. Cancer Research UK © 2010.. [Updated April 2010, accessed 2010 October 6].Available here.
6. Roy Castle Lung Cancer Foundation © 2010. About Lung Cancer – Types of lung cancer [Updated 2007, accessed 2010 October 6]. Available here.
7. Press Release from the National Cancer Research Institute 10.10.06.Available here.