Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study.
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Colorectal Neoplasms
/ drug therapy
DNA Mismatch Repair
DNA Repair Enzymes
/ deficiency
Female
Fluorouracil
/ therapeutic use
Humans
Irinotecan
/ administration & dosage
Male
Microsatellite Instability
Middle Aged
Neoplasm Metastasis
Oxaliplatin
/ administration & dosage
Prognosis
Progression-Free Survival
Retrospective Studies
Survival Analysis
Young Adult
chemosensitivity
colorectal cancer
deficient mismatch repair
metastatic
microsatellite instability
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
27
09
2019
revised:
19
12
2019
accepted:
07
01
2020
pubmed:
24
1
2020
medline:
24
3
2021
entrez:
24
1
2020
Statut:
ppublish
Résumé
Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.
Substances chimiques
Oxaliplatin
04ZR38536J
Irinotecan
7673326042
DNA Repair Enzymes
EC 6.5.1.-
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
285-296Informations de copyright
© 2020 UICC.
Références
Kolligs FT. Diagnostics and epidemiology of colorectal cancer. Visc Med 2016;32:158-64.
Weisenberger DJ, Siegmund KD, Campan M, et al. CpG Island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006;38:787-93.
Tougeron D, Sickersen G, Mouillet G, et al. Gastro-Entérologues Oncologues (AGEO). Predictors of disease-free survival in colorectal cancer with microsatellite instability: an AGEO multicentre study. Eur J Cancer 2015;51:925-34.
Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247-57.
Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010;28:3219-26.
Tougeron D, Mouillet G, Trouilloud I, et al. Efficacy of adjuvant chemotherapy in colon cancer with microsatellite instability: a large multicenter AGEO study. J Natl Cancer Inst 2016;108:djv438.
André T, de Gramont A, Vernerey D, et al. Adjuvant fluorouracil, Leucovorin, and Oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol 2015;33:4176-87.
Venderbosch S, Nagtegaal I, Maughan T, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 2014;20:5322-30.
Des Guetz G, Uzzan B, Nicolas P, et al. Microsatellite instability does not predict the efficacy of chemotherapy in metastatic colorectal cancer. A systematic review and meta-analysis. Anticancer Res 2009;29:1615-20.
Goldstein J, Tran B, Ensor J, et al. Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability. Ann Oncol 2014;25:1032-8.
Cohen R, Buhard O, Cervera P, et al. Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency. Eur J Cancer 2017;86:266-74.
de la Fouchardière C, Cohen R, Malka D, et al. Characteristics of BRAF V600E mutant, deficient mismatch repair/proficient mismatch repair, metastatic colorectal cancer: a multicenter series of 287 patients. Oncologist 2019;24:e1331-40.
Yu Y, Ying J, Zhang W, et al. Outcome of chemotherapy with or without targeted agents in metastatic colorectal cancer patients with deficient DNA mismatch repair: a single center, cohort study. Asia Pac J Clin Oncol 2019;15:128-35.
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-20.
Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with Nivolumab plus Ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol 2018;36:773-9.
Buhard O, Cattaneo F, Wong YF, et al. Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol 2006;24:241-51.
Suraweera N, Duval A, Reperant M, et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 2002;123:1804-11.
Austin PC, Schuster T. The performance of different propensity score methods for estimating absolute effects of treatments on survival outcomes: a simulation study. Stat Methods Med Res 2016;25:2214-37.
Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 2011;117:4623-32.
Lochhead P, Kuchiba A, Imamura Y, et al. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J Natl Cancer Inst 2013;105:1151-6.
Golan T, Urban D, Berger R, et al. Changing prognosis of metastatic colorectal adenocarcinoma: differential improvement by age and tumor location. Cancer 2013;119:3084-91.
Taieb J, Pederson L, Shi Q, et al. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence: results of an accent meta-analysis of seven studies. Ann Oncol 2019;30:1466-71.
Jin Z, Sanhueza CT, Johnson B, et al. Outcome of mismatch repair-deficient metastatic colorectal cancer: the Mayo Clinic experience. Oncologist 2018;23:1083-91.
Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 on the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229-37.
Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with Cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA 2017;317:2392-401.
Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014;15:1065-75.
Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:2013-9.
Lenz H-JJ, van Cutsem E, Limon ML, et al. Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Ann Oncol 2018;29:mdy424.019.
Kim ST, Kim HK, Lee J, et al. The impact of microsatellite instability status and sidedness of the primary tumor on the effect of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer. J Cancer 2018;9:1791-6.
Kim ST, Lee SJ, Lee J, et al. The impact of microsatellite instability status and sidedness of the primary tumor on the effect of Cetuximab-containing chemotherapy in patients with metastatic colorectal cancer. J Cancer 2017;8:2809-15.
Kim JE, Hong YS, Ryu MH, et al. Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer. Cancer Sci 2011;102:1706-11.
Kim ST, Lee J, Park SH, et al. The effect of DNA mismatch repair (MMR) status on oxaliplatin-based first-line chemotherapy as in recurrent or metastatic colon cancer. Med Oncol 2010;27:1277-85.
Alex AK, Siqueira S, Coudry R, et al. Response to chemotherapy and prognosis in metastatic colorectal cancer with DNA deficient mismatch repair. Clin Colorectal Cancer 2017;16:228-39.
des Guetz G, Mariani P, Cucherousset J, et al. Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer. Anticancer Res 2007;27:2715-9.
Fallik D, Borrini F, Boige V, et al. Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 2003;63:5738-44.
Innocenti F, Ou FS, Qu X, et al. Mutational analysis of patients with colorectal cancer in CALGB/SWOG 80405 identifies new roles of microsatellite instability and tumor mutational burden for patient outcome. J Clin Oncol 2019;37:1217-27.
Holch JW, Ricard I, Stintzing S, et al. The relevance of primary tumour location in patients with metastatic colorectal cancer: a meta-analysis of first-line clinical trials. Eur J Cancer 2017;70:87-98.