656 - Survival outcomes in metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H)

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Michael Overman
Authors M.J. Overman1, S. Kopetz1, S. Wong2, J. Tie2, S. Kosmider2, A. Jacob1, E. Vilar3, P. Gibbs2, J. Desai2, B. Tran2
  • 1Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Medical Oncology, Royal Melbourne Hospital, Melbourne/AU
  • 3Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, 77030 - Houston/US



The MSI-H phenotype is present in 15% of early stage CRC and confers good prognosis in this population. In metastatic CRC, MSI-H is rare and its impact on outcomes is unknown. We describe survival outcomes and responses to chemotherapy for the largest reported cohort of MSI-H metastatic CRC.


A retrospective review of metastatic CRC patients (pts) with MSI-H (defined as ≥2 DNA microsatellite markers with instability by PCR) from two institutions was conducted. Pts from Royal Melbourne Hospital (Australia) were identified using a prospective CRC database. Pts from The University of Texas MD Anderson Cancer Center (United States) were identified from an institutional database. Statistical analyses utilized Kaplan-Meier method and Log-rank test.


55 pts with metastatic MSI-H CRC were identified. Median age was 67 years (range: 20-90), 63% had poor differentiation, and 64% of primary tumors originated in the right colon. 25 (45%) pts had stage IV disease at presentation, while 30 (55%) pts presented with stage II/III disease (median time to development of metastases was 9 months). 42 pts have died and median overall survival (OS) from the time of metastatic disease was 15.3 months. 14 pts underwent R0/R1 metastatectomies with median time to recurrence of 25.4 months and median OS from metastatectomy of 33.7 months. 31 pts were evaluable for response to front-line systemic chemotherapy: single agent 5-FU in 7, oxaliplatin-based in 14, and irinotecan-based in 10. Radiographic response was seen in 11 pts (35%) and the median time to progression (TTP) and OS were 4.2 months and 11.6 months, respectively. No statistically significant differences in TTP or OS were seen between chemotherapy subtypes. BRAF mutation status was known in 47 pts: 14 pts had a BRAF V600E mutation, 33 pts were wildtype (wt). In comparison to BRAF wt pts, BRAF V600E pts demonstrated significantly worse median OS; 10.1 v 17.4 months, HR 2.6 (95%CI: 1.1-6.1), P =0.03.


Compared to historical controls, pts with MSI-H metastatic CRC do not appear to have improved outcomes. BRAF V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.


All authors have declared no conflicts of interest.