The 12-Gene Colon Cancer Recurrence Score (RS) Predicts Recurrence in Stage II and III Colon Cancer Patients Treated with 5FU/LV (FU) and 5FU/LV + Oxaliplatin (FU + OX): Validation in NSABP C07

ABSTRACT Background Standardized tools which accurately quantify recurrence risk are needed for optimal adjuvant treatment of colon cancer. The 12-gene RS has been validated in stage II colon cancer pts from QUASAR and CALGB 9581. We conducted a large prospectively-designed clinical validation study of RS, w/ pre-specified endpoints, methods, and analysis plan, in stage II and III colon cancer pts randomized to FU or FU + Ox in C-07. Methods 50% of C-07 pts w/ tissue were randomly selected, stratified on stage and recurrence. Gene expression was quantitated by RT-PCR on 25 µm manually microdissected fixed tumor tissue. Data were analyzed by Cox regression controlling for stage and treatment (TRT). Results RT-PCR was successful in 892/921 pts (97%): 449 FU, 443 FU + Ox; 264 st II, 409 st IIIA/B, 219 st IIIC. The primary endpoint was met: RS predicted recurrence (HR/25 units = 1.96, 95% CI 1.50-2.55 p  Conclusions RS predicts recurrence risk in stage II and III colon cancer, capturing underlying biology and providing risk information beyond conventional factors. RS is not predictive of relative Ox benefit but enables better discrimination of absolute Ox benefit as a function of risk. Incorporating RS into the clinical context may better inform adjuvant therapy decisions for pts w/ stage III as well as stage II colon cancer. Disclosure M. Lee: I am an employee and stockholder of Genomic Health, Inc. M. Lopatin: I am an employee and stockholder of Genomic Health, Inc. K.M. Clark-Langone: I am an employee and stockholder of Genomic Health, Inc. C. Millward: I am an employee and stockholder of Genomic Health, Inc. S. Shak: I am Chief Medical Officer and a stockholder of Genomic Health, Inc. All other authors have declared no conflicts of interest.