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

Filippo Pietrantonio, Rosalba Miceli, Alessandra Raimondi, Young Woo Kim, Won Ki Kang, Ruth E. Langley, Yoon Young Choi, Kyoung Mee Kim, Matthew Guy Nankivell, Federica Morano, Andrew Wotherspoon, Nicola Valeri, Myeong Cherl Kook, Ji Yeong An, Heike I. Grabsch, Giovanni Fucà, Sung Hoon Noh, Tae Sung Sohn, Sung Kim, Maria Di BartolomeoDavid Cunningham, Jeeyun Lee, Jae Ho Cheong, Elizabeth Catherine Smyth

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3392-3400
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number35
DOIs
Publication statusPublished - Dec 10 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pietrantonio, F., Miceli, R., Raimondi, A., Kim, Y. W., Kang, W. K., Langley, R. E., Choi, Y. Y., Kim, K. M., Nankivell, M. G., Morano, F., Wotherspoon, A., Valeri, N., Kook, M. C., An, J. Y., Grabsch, H. I., Fucà, G., Noh, S. H., Sohn, T. S., Kim, S., ... Smyth, E. C. (2019). Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 37(35), 3392-3400. https://doi.org/10.1200/JCO.19.01124