Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.
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Date
2019-12-10ICR Author
Author
Pietrantonio, F
Miceli, R
Raimondi, A
Kim, YW
Kang, WK
Langley, RE
Choi, YY
Kim, K-M
Nankivell, MG
Morano, F
Wotherspoon, A
Valeri, N
Kook, M-C
An, JY
Grabsch, HI
Fucà, G
Noh, SH
Sohn, TS
Kim, S
Di Bartolomeo, M
Cunningham, D
Lee, J
Cheong, J-H
Smyth, EC
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value. PATIENTS AND METHODS: We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery v surgery) with MSI. RESULTS: MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio [HR], 1.88; 95% CI, 1.28 to 2.76; P < .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73; P = .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12). CONCLUSION: In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.
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Subject
Humans
Stomach Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Chemotherapy, Adjuvant
Survival Rate
Follow-Up Studies
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Microsatellite Instability
Young Adult
Biomarkers, Tumor
Precision Medicine
Research team
Medicine (RMH Smith Cunningham)
Gastrointestinal Cancer Biology and Genomics
Language
eng
License start date
2019-12
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, 37 (35), pp. 3392 - 3400
Publisher
LIPPINCOTT WILLIAMS & WILKINS