PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer--results from NCIC CTG/AGITG CO.17.
作者： Christos S Karapetis , Derek Jonker , Manijeh Daneshmand , Jennifer E Hanson , Christopher J O'Callaghan
DOI: 10.1158/1078-0432.CCR-13-0606
关键词: Colorectal cancer 、 PTEN 、 Internal medicine 、 Medicine 、 Cetuximab 、 Population study 、 Biomarker (medicine) 、 Cancer 、 Proportional hazards model 、 Tissue microarray 、 Cancer research 、 Oncology
摘要: Purpose: Cetuximab improves survival in patients with K-ras wild-type advanced colorectal cancer. We examined the predictive and prognostic significance of additional biomarkers this setting, particular BRAF , PIK3CA PTEN. Experimental Design: Available tumor samples were analyzed from CO.17 study. mutations identified tumor-derived DNA by direct sequencing using a high-resolution melting screen confirmation sequencing. PTEN expression immunohistochemistry (IHC) was performed on tissue microarrays. For each biomarker, effects Cox model tests for treatment–biomarker interaction. Results: A total 572 pretreated cancer randomly assigned to receive cetuximab or best supportive care (BSC). Of 401 assessed status, 13 (3.2%) had mutations. 407 61 (15%) 205 PTEN, 148 (72%) negative IHC expression. None overall progression-free BSC arm. benefit cetuximab, either whole study population subset. In subgroup, adjusted HR according mutation status 1.39 (interaction P = 0.69), 0.79 0.63), 0.75 0.61). Conclusions: chemotherapy-refractory cancer, neither nor prognostic, they cetuximab. Evaluation requires larger sample size. Clin Cancer Res; 20(3); 744–53. ©2013 AACR .
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