Association between deficient mismatch repair system and efficacy to irinotecan containing first-line chemotherapy in patients with sporadic metastatic colorectal cancer.

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3579 Background: Colorectal cancer with deficient mismatch repair system (dMMR) has been associated with favorable prognosis in early-stage disease. The influence of dMMR on response to chemotherapy in metastatic colorectal cancer (mCRC) has not been fully defined yet. The aim of our study was to investigate the association between dMMR and efficacy outcomes to irinotecan-based first-line chemotherapy in patients (pts) with mCRC. Methods: Between January 2004 and April 2008, about 297 pts with sporadic mCRC received irinotecan-containing regimen as their first-line chemotherapy. Paraffin-embedded tissues were available in 200 pts and were included in this study. Expression of mismatch repair proteins was examined by immunohistochemistry and treatment outcomes were retrospectively reviewed. The tumors were defined dMMR if at least one of the MLH1 or MSH2 showed negative expression and others defined proficient MMR (pMMR). Response rate (RR), disease control rate (DCR), and progression-free survival (PFS) were compared between pts with dMMR and pMMR. Results: Deficient mismatch repair was found in 23 (11.5%) out of 200 evaluable pts of which 8 showed negative MLH1 expression, 11 showed negative MSH2, and 4 showed negative expressions in two of all. The overall RR was 47%; 45.8% (81/177) in pMMR and 56.5% (13/23) in dMMR, respectively, and there was no statistical difference between two groups (Table). The median PFS tended to be longer with 8.85 months (mo) (95% confidence interval [CI], 7.06-10.64) in pts with dMMR tumors compared to 6.82 mo (95% CI, 6.15-7.49) in pts with pMMR tumors, but the difference was not statistically significant (p=0.092). Conclusions: Efficacy outcomes to first-line irinotecan-based chemotherapy were not statistically different in mCRC pts either with pMMR or dMMR, but a trend toward longer PFS was observed in patients with dMMR. pMMR (n = 177) dMMR (n = 23) P value ORR 81 (45.8%) 13 (56.5%) 0.110 DCR (PR + SD) 138 (78.0%) 20 (87.0%) 0.145 PFS (mo) 6.82 mo 8.85 mo 0.092 No significant financial relationships to disclose.

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