Abstract
6081 Background: We studied the addition of C to a sequential regimen of weekly CBDCA and P followed by CBDCA-P-radiation in pts with locally advanced resectable HNSCC. Tissue-based biomarkers may aid in pt selection for such approaches. Methods: Sixty-three eligible pts withoperablestage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly C, P and CBDCA x 6 followed by CRT with concurrent weekly C, paclitaxel, carboplatin. A tissue microarray was constructed and b-catenin, E-cadherin, Epidermal Growth Factor Receptor Variant III (EGFRVIII), insulin-like growth factor-1 receptor (IGF1R), NF-kappa b, p53, PI3Kp85, PI3Kp110a, PTEN, ΝRAS, and pRb protein expression levels were assessed using automated quantitative protein analysis (AQUA). For each marker, time-to-event distributions (OS, PFS, and EFS) were estimated by Kaplan-Meier estimates and compared using log-rank tests. Multivariable Cox proportional hazards models were used to estimate hazard ratios and test for significance, with primary site (oropharynx vs. non-oropharynx), disease stage (III vs. IV), and other important markers adjusted in the model. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: Based on the continuous scale, pRb tended to association with EFS (p=0.05). On multivariable analysis, low pRb level was a significant predictor for improved EFS (p=0.048). Our pRb data analysis was based on 32 pts with marker data available. Conclusions: pRb level is a potential predictive biomarker for response to cetuximab. HPV E7 oncoprotein binds and degrades pRb; therefore, low pRb protein level might be a surrogate marker for HPV association.Large prospective studies will be required to determine the association between pRb, HPV status and response to cetuximab in HNSCC.
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