Open AccessConsequences of a high incidence of microsatellite instability and BRAF‐ mutated tumors: A population‐based cohort of metastatic colorectal cancer patients
Author(s) -
Aasebø Kristine Ø.,
Dragomir Anca,
Sundström Magnus,
Mezheyeuski Artur,
Edqvist PerHenrik,
Eide Geir Egil,
Ponten Fredrik,
Pfeiffer Per,
Glimelius Bengt,
Sorbye Halfdan
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2205
Subject(s) - microsatellite instability , colorectal cancer , medicine , oncology , chemotherapy , cohort , population , cancer , microsatellite , allele , biology , gene , environmental health , biochemistry
Background Immunotherapy for patients with microsatellite‐instable (MSI‐H) tumors or BRAF ‐inhibitors combination treatment for BRAF‐ mutated (mut BRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population‐based studies of these molecular changes are warranted. Methods A population‐based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression‐free survival (PFS) were estimated. Results Here, 40/583 (7%) tumor samples were MSI‐H and 120/591 (20%) were mut BRAF ; 87% of MSI‐H tumors were mut BRAF (non‐Lynch) . Elderly (>75 years) had more often MSI‐H (10% vs 6%) and MSI‐H/mut BRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first‐line chemotherapy was all significantly lower in patients with MSI‐H compared to patients with microsatellite stable tumors. MSI‐H and mut BRAF were both independent poor prognostic predictors for OS ( P = 0.049, P < 0.001) and PFS ( P = 0.045, P = 0.005) after first‐line chemotherapy. Patients with MSI‐H tumors received less second‐line chemotherapy (15% vs 37%, P = 0.005). Conclusions In unselected mCRC patients, MSI‐H and mut BRAF cases were more common than previously reported. Patients with MSI‐H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third‐line immunotherapy trial patients as they were older and most had mut BRAF tumor (non‐Lynch).