%0 Journal Article
%T A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy
%A Wei Chen
%A Gerold Bepler
%J Journal of Personalized Medicine
%D 2013
%I MDPI AG
%R 10.3390/jpm3030251
%X Platinum-based chemotherapy is a primary treatment of choice for advanced non-small-cell lung cancer (NSCLC). Analytical methods to specifically evaluate biomarkers predictive of therapeutic efficacy have not been developed. Two randomized phase III trials of carboplatin-based chemotherapy in advanced NSCLC were used for learning and validating the predictive value of ERCC1 in situ protein levels, as measured by accurate quantitative analysis (AQUA). A novel Bayesian method was applied to identify the outcome-based threshold in the learning trial only. Overall survival (OS) was assessed by Kaplan-Meier analysis with log rank testing to determine statistical significance in the validating trial. For patients treated with gemcitabine and carboplatin, the median OS was 9.5 months (95% CI 6.7 to 11.8) for the high ERCC1 group compared to 15.6 months (95% CI 11.6 to 24.8) for the low ERCC1 group in the validation trial (log rank p-value = 0.007). The hazard ratio for low ERCC1 was 0.598 (95% CI, 0.394 to 0.908; p = 0.016) relative to high ERCC1 adjusted for age, sex, and histology. Conclusions: Patients with advanced NSCLC could be stratified into high and low ERCC1 expression groups. Patients with low levels benefited from platinum-based chemotherapy, whereas those with high levels did not.
%K biomarkers
%K cancer
%K protein expression
%K methodology
%K non-small-cell lung cancer
%K ERCC1
%U http://www.mdpi.com/2075-4426/3/3/251