Microsatellite instability and sensitivity to fluoropyrimidine and oxaliplatin containing first-line chemotherapy in metastatic colorectal cancer

Abstract

ObjectivesTo examine the effect of microsatellite instability (MSI) on the outcome of fluoropyrimidine and oxaliplatin containing first-line chemotherapy in metastatic colorectal cancer (mCRC).MethodsPatients with mCRC and treated with fluoropyrimidine/oxaliplatin first-line chemotherapy were included in our study. Demographic data, tumour characteristics, chemotherapy regimens, treatment responses and progression-free survival (PFS) were collected from medical records. The MSI analysis was performed using fluorescence-based PCR, and divided into MSI-high (MSI-H) and MSI-low (MSI-L)/microsatellite stable (MSS). Statistical analysis used Kaplan-Meier method, log-rank test and multivariate Cox model.ResultsFrom 1 January 2015 to 1 May 2016, a total of 192 patients with mCRC were included in our study. Among these, 14 (7.29%) exhibited MSI-H and 178 (92.71%) were MSI-L/MSS. The objective response rate (p=0.79), disease control rate (p=0.22) and PFS (p=0.22) of fluoropyrimidine/oxaliplatin first-line chemotherapy were not significantly different between MSI-H and MSI-L/MSS tumours. But MSI-H tumours had a trend to better disease control rate (71.43% vs 54.49%) and PFS (6.50 m vs 5.40 m) than MSI-L/MSS tumours. Multivariate analysis indicated that MSI was not a predictive factor for PFS (p=0.18).ConclusionThe effect of fluoropyrimidine/oxaliplatin first-line chemotherapy was not significantly different between MSI-H and MSI-L/MSS tumours. However, MSI-H tumours tended to have better disease control rate and PFS.

Clinical impact of primary tumor sidedness and sex on unresectable post-recurrence survival in resected pathological stage II-III colorectal cancers: a nationwide multicenter retrospective study

“…Furthermore, BRAF mutation was observed more frequently in females and proximal tumors [ 22 ]. MSI-high cancer is associated with the proximal colon and females, and is a predictive marker for fluoropyrimidine/oxaliplatin first-line chemotherapy [ 23 ]. Significantly, the rates of TP53 mutations increase as they are located distally [ 39 ], and TP53 mutation is more frequent in sporadic cancers among males than females [ 24 ].…”

Current Systemic Treatments for the Hereditary Cancer Syndromes: Drug Development in Light of Genomic Defects

“…In patients with Lynch syndrome, there had previously been dual concerns about the lessened efficacy of fluoropyrimidines (at least as monotherapy 74 ) and thus the need for intensified exposure to partner drugs like platinums, 75 which then incurred the very real threat of irreversible toxicities like chemotherapy-induced peripheral neuropathy in patients with a > 80% lifetime risk of developing colorectal cancer. 76 Whereas the prior U.S. Food and Drug Administration approval of pembrolizumab in high microsatellite instability metastatic colorectal cancer in 2017 had required "progress[ion] following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan," with the advent of KEYNOTE-177 in 2020, patients with Lynch syndrome could finally be treated with a truly chemotherapy-free approach, mitigating their greatest risk of cancer-related death while better preserving quality of life.…”

ATG16L2 overexpression is associated with a good prognosis in colorectal cancer

“…Clinically, even for patients who undergo thorough surgery at an early stage, the postoperative pathological grade is high and the prognosis Original Article ATG16L2 overexpression is associated with a good prognosis in colorectal cancer poor (5). This phenomenon suggests that the efficacy of chemotherapy depends not only on the tumor stage and pathological type, but also on other factors (6). Therefore, early prognostic assessment is the most effective way to improve survival and assess tumor progression in patients with CRC.…”