P2.03b-054 Biomarker Predictors in NSCLC: Topic: Biomarkers

Among the major challenges in the chemotherapeutic regimens is lacking of effective biomarkers for drug response and sensitivity. Our current study reviewed two promising biomarkers, ERCC1 (excision repair cross-complementing group 1) and RRM1 (ribonucleotide reductase group 1) to identify their potentiality to predict responder to Cisplatin and Gemcitabine among NSCLC (Non-Small Cell Lung Cancer) patients. Prospectively, this study was conducted in National Cancer Institute (NCI) Cairo, Egypt. We measured the mRNA expression level of ERCC1 and RRM1 in tumor cells (using Real-time quantitative PCR) isolated from Stage IIIB/IV NSCLC patients planned to receive Cisplatin and Gemcitabine. Patients were divided into two groups, either both low ERCC1 and RRM1 (group 1) or both are high (group 2). Our objectives were the correlation between both groups and clinical response (CR), Progression free survival (PFS) and Overall Survival (OS). 55 patients were enrolled and followed from Jan 2011 to Jan 2014, Median age was 57(30-75years), 87% had ECOG-PS1, 86% had stage IV, responder (SD/PR) represented 56%. 30 patients had both low ERCC1 and RRM1 (group 1) while the rest 25 patients had high ERCC1 and RRM1 (group 2). There was no significant differences between different clinical response in both groups (P= 0.239), however multivariate Cox regression analysis revealed responders (p=0.007, HR0.33) and high ERCC1/RRM1 RNA (p=0.032, HR;2.51) to be the only predictors of overall survival. Patients in group 1 had longer median PFS (9.8 ms vs 4.9 ms, P= 0.001) and longer median OS (12.5 ms vs 6.2 ms, P<0.001) than patients in group 2. Low ERCC and RRM1 RNA levels serve as a guidance to predict chemosensitivity to cisplatin and Gemcitabine, with longer survival. Combination of ERCC1 and RRM1 RNA has a prognostic and predictive significance in Stage IIIB/IV NSCLC patients receiving Cisplatin and Gemcitabine. Large cohort studies are warranted.