MSI-H AND AVASTIN BENEFIT

J Natl Cancer Inst. 2013 Jul 3;105(13):989-992.

Defective Mismatch Repair and Benefit from Bevacizumab for Colon Cancer: Findings from NSABP C-08.

Pogue-Geile K, Yothers G, Taniyama Y, Tanaka N, Gavin P, Colangelo L, Blackmon N, Lipchik C, Kim SR, Sharif S, Allegra C, Petrelli N, O'Connell MJ,Wolmark N, Paik S.

Source

Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA (KP-G, GY, YT, NT, PG, LC, NB, CL, SRK, SS, CA, NP, MJO, NW, SP); NSABP Biostatistical Center, Pittsburgh, PA (GY, LC); Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (GY, LC); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (SS, NW); Department of Medicine, University of Florida Shands Cancer Center, Gainesville, FL (CA); Helen F. Graham Cancer Center at Christiana Care, Newark, DE (NP); Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul, South Korea (SP).

Abstract

National Surgical Adjuvant Breast and Bowel Project protocol C-08 tested the worth of adding 1 year of bevacizumab to oxaliplatin-based standard adjuvant chemotherapy regimen in the treatment of stage II/III colon cancer. Although the overall result was negative, the possibility that a molecularly defined subset could benefit from bevacizumab cannot be ruled out. We performed post hoc Cox regression analyses to test for marker-by-treatment interactions for standard pathological features and survival analyses using the Kaplan-Meier method. All statistical tests were two-sided and considered statistically significant at the .05 level. Patients diagnosed with mismatch repair defective (dMMR) tumors derived statistically significant survival benefit from the addition of bevacizumab (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.29 to 0.94; P = .02) in contrast with no benefit in patients diagnosed with mismatch repair proficient tumors (HR = 1.03; 95% CI = 0.84 to 1.27; p = .78; P _interaction = .04). Although a post hoc finding, this data suggests that a molecularly defined subset of colon cancer patients may derive clinical benefit from antiangiogenesis agents and underscores the need for independent validation in other clinical trials.