523PD - 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 + o...

Date 29 September 2012
Event ESMO Congress 2012
Session Gatrointestinal tumors, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Presenter Michael O'Connell
Authors M.J. O'Connell1, M. Lee2, M. Lopatin3, G. Yothers4, K.M. Clark-Langone5, C. Millward6, S. Paik1, S. Sharif1, S. Shak7, N. Wolmark1
  • 1Nsabp, National Surgical Adjuvant Breast and Bowel Project, 15212 - Pittsburgh/US
  • 2Genomic Health, Inc., 94063 - Redwood City/US
  • 3Biostatistics, Genomic Health, Inc., Redwood City/US
  • 4Biostatistical Center, NSABP, Pittsburgh/US
  • 5Development Laboratory, Genomic Health, Inc., Redwood City/US
  • 6Pathology, Genomic Health, Inc., Redwood City/US
  • 7Oncology Development, Genomic Health, Inc., 94063 - Redwood City/US

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 < .001). RS also predicted DFS (p < .001) and OS (p < .001). RS predicted recurrence (p = .001) independent of T and N stage, MMR, nodes examined, grade, and TRT. Predefined high RS group (25% of pts) had higher recurrence risk than low RS group (39% of pts): HR = 2.11, p < .001. Cox model 5 yr recurrence risk (95%CI) in FU treated pts by RS group (low, high): st II 9% (6-13%), 18% (12-25%); st IIIA/B 21% (16-26%), 38% (30-46%); st IIIC 40% (32-48%), 64% (55-74%). RS did not have significant interaction w/ stage (p = 0.90) or age (p = 0.76). Relative Ox benefit was similar across range of RS (interaction p = 0.48); accordingly, in Cox model and Kaplan-Meier analyses, absolute Ox benefit increased w/ higher RS. In an exploratory analysis of 735 genes, 16 genes were identified as associated with relative Ox benefit after controlling false discovery rate at 20%.

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.