Year: 2011
Type: editorial
Abstract: There are intense commercial pressures in industry to develop drugs for large unselected populations, although this remains a risky and expensive strategy. Several examples now exist where targeted treatments are utilised in molecularly defined cancer patient populations. The EGFR tyrosine kinase inhibitor (TKI) gefitinib is a case in point, failing to show a clear benefit in non-small-cell lung cancer (NSCLC) patients when given with first-line chemotherapy. Gefitinib has nevertheless re-emerged as an important therapeutic following the confirmation that mutations in the TK domain of EGFR confer sensitivity to it ( Mok et al, 2009 ), with evidence that this population is enriched within Asian, female and never-smoker patients with adenocarcinoma ( Lynch et al, 2004 ; Paez et al, 2004 ). More recently, two large-phase III trials, investigating the addition of the fully human monoclonal antibody (mAb) to the insulin-like growth factor 1 receptor (IGF-1R) figitumumab (CP-751,871, Pfizer) to carboplatin/paclitaxel (ADVIGO 1016) and to the EGFR TKI erlotinib (ADVIGO 1018), in advanced NSCLC patients have been suspended after planned interim analyses indicated futility ( Jassem et al, 2010 ). These data raise several important questions: Was there sufficient evidence to support these phase III trials? Could we have learnt more from early-phase data to identify the patients who are most likely to benefit? Is IGF-1R a key target in NSCLC? How should we design our trials to identify predictive biomarkers that decrease the risk of such late and costly failures?
Source: British Journal of Cancer
Authors: B Basu, D Olmos, J S de Bono
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W2095275496