Impact of KRAS, BRAF, PIK3CA Mutations, PTEN, AREG, EREG Expression and Skin Rash in ≥2nd Line Cetuximab-Based Therapy of Colorectal Cancer Patients

摘要: Background To investigate the predictive significance of KRAS, BRAF, PIK3CA mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in metastatic colorectal cancer (mCRC) patients treated with cetuximab containing salvage chemotherapy. Methods Primary tumors from 112 mCRC were analyzed. The worst toxicity during treatment was recorded. Results KRAS, BRAF mutations present 37 (33%), 8 (7.2%) 11 (9.8%) cases, respectively, lost 21 (19.8%) AREG overexpressed 48 (45%) 51 (49%) cases. In whole study population, time to tumor progression (TTP) overall survival (OS) significantly lower KRAS (p = 0.001 p 0.026, respectively) or p<0.0001, mutant tumors, downregulation 0.018 0.013, 0.002 0.004, grade 0-1 (p<0.0001 respectively). wt TTP OS 0.0001 0.021 0.01) 0.002). Multivariate analysis revealed (Hazard Ratio [HR] 4.3, p<0.0001), mutation (HR: 5.1, low 1.6, 0.021) absence severe/moderate 4.0, p<0.0001) as independent prognostic factors for decreased TTP. Similarly, (HR 2.9, 0.01), 3.0, 0.001), 1.7, 0.021), absecence 3.7, presence undifferantited tumours 2.2, 0.001) OS. Conclusions These results underscore that KRAS-BRAF can be used biomarkers further select undergoing anti-EGFR treatment.