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J Clin Oncol. 2019 Sep 12:JCO1901124. doi: 10.1200/JCO.19.01124. [Epub ahead of print]

Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.

Author information

1
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
2
University of Milan, Milan, Italy.
3
National Cancer Center, Goyang, Korea.
4
Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
5
The Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom.
6
Yonsei University College of Medicine, Seoul, Korea.
7
The Institute of Cancer Research, London, United Kingdom.
8
GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
9
Leeds Institute for Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
10
Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

Abstract

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.

PMID:
31513484
DOI:
10.1200/JCO.19.01124

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