A large retrospective multicenter study evaluating prognosis and chemosensitivity of metastatic colorectal cancer with microsatellite instability

Background: Deficient Mismatch Repair (dMMR) and/or microsatellite instability-high colorectal cancers (CRC) represent 12% of all tumors. dMMR non-metastatic CRC are associated with good prognosis but also with resistance to adjuvant 5FU. dMMR metastatic CRC (mCRC) is found in 5% and its influence on prognosis and chemosensitivity is little known. Methods: This multicenter study included patients with dMMR mCRC treated between 2005 and 2015 in 18 French centers. The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS). Prognostic variables were evaluated in univariate (Log rank test) and multivariate analyses (Cox regression model). Results: 284 patients with dMMR mCRC were included. Lynch syndrome was found in 43% and BRAF mutation in 32%. Median OS was 25.0 months. Peritoneal carcinomatosis (p < 0.01) and surgery of metastasis (p < 0.01) were associated with OS in multivariate analysis but not BRAF mutation and Lynch syndrome. 37% of patients had surgery of metastasis, 79% received first-line chemotherapy (palliative or peri-operative), 46% second-line, 16% third-line. First-line regimens were 5FU-based (n = 20), oxaliplatin-based (n = 106) or irinotecan-based (n = 82) without or with anti-VEGF (n = 71) or anti-EGFR (n = 34). Median PFS on first-line chemotherapy was 5.7 months and in multivariate analysis only surgery of metastasis was associated with PFS (p < 0.01). Median PFS and OS on palliative first-line chemotherapy (n = 149) were 3.9 months and 17.9 months. Median PFS (3.9, 4.4 and 3.0 months, p = 0.20) and OS (17.9, 16.8 and 23.9 months, p = 0.14) were not different according chemotherapy regimen (5FU-based, oxaliplatin-based and irinotecan-based). The addition of bevacizumab or anti-EGFR therapy were associated with a non-significant increased of PFS as compared to chemotherapy alone (4.6, 6.0 and 3.5 months, p = 0.06). In second-line, median PFS and OS were 3.5 months and 15.8 months. In third-line, median OS was 6.3 months. Conclusions: This study suggests that dMMR mCRC are associated with poor prognosis with conventional chemotherapy with or without bevacizumab or anti-EGFR. Only surgery of metastasis was associated with better PFS. Legal entity responsible for the study: Tougeron David Funding: None Disclosure: D. Tougeron: Consulting or advisory role for Amgen, Sanofi, Celgene. Travel or accommodation from Ipsen, Amgen, Sanofi. J. Taieb: Honoraria: Amgen, Merck, Roche, Baxalta, Celgene, Sanofi, Lilly, Sirtex. T. André: Honoraria: Roche, Bms, Sanofi. All other authors have declared no conflicts of interest.