Prognostic Impact of Microsatellite Instability in Asian Gastric Cancer Patients Enrolled in the ARTIST Trial

Miceli, Rosalba; An, Ji-Yeong; Bartolomeo, Maria Di; Morano, Federica; Kim, Seung Tae; Park, Se Hoon; Choi, Min Gew; Lee, Woo Jung; Raimondi, Alessandra; Fucà, Giovanni; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Lim, Do Hoon; Kang, Won Ki; Kim, Kyoung‐Mee; Pietrantonio, Filippo; Lee, Jeeyun

doi:10.1159/000499628

Cited by 34 publications

(22 citation statements)

References 13 publications

(16 reference statements)

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“…The selected population from each trial was not notably different from the corresponding whole-trial population, as reported previously. [13][14][15]22 Baseline patients and disease characteristics are listed in the Data Supplement. Briefly, two trials (CLASSIC and ARTIST) were conducted in Asian countries, and two others (MAGIC and ITACA-S) were performed on a European population.…”

Section: Resultsmentioning

confidence: 99%

“…2,3,16,17 In addition, post hoc analyses of all trials aimed at investigation of the interaction between MSI status and patient outcome have already been presented. [13][14][15]18 The purpose of this study was to assess the potential prognostic role of MSI status in patients with radically resected GC and its potential value to predict the outcome to systemic treatment in this patient population.…”

Section: Study Design and Trial Populationsmentioning

confidence: 99%

“…14 Despite these results from historically important randomized clinical trials (RCTs), a significant challenge for the adoption of MSI/mismatch repair deficiency testing as a routine biomarker in patients with operable GC is the low MSI prevalence in GC (8% to 10%), which led to limited statistical power of the observations in individual trial data sets. [13][14][15] With this in mind, we pooled individual patient data from four large, multinational RCTs performed in patients with resectable GC (MAGIC, 3 CLASSIC, 2 ARTIST, 16 and ITACA-S 17 ), and evaluated the relationship between MSI status, overall survival (OS), and DFS and biomarker interaction with chemo(radio)therapy treatment.…”

Section: Introductionmentioning

confidence: 99%

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

Pietrantonio

Miceli

Raimondi

et al. 2019

JCO

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350

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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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Section: Resultsmentioning

confidence: 99%

Section: Study Design and Trial Populationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Pietrantonio

Miceli

Raimondi

et al. 2019

JCO

Self Cite

350

246

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“…However, it remains difficult to determine whether the survival benefit is a result of cytotoxic treatment or due to an inherent prognostic advantage. Furthermore no significant interaction between MSI status and radiotherapy was seen when patients were treated with adjuvant chemotherapy (capecitabine and cisplatin) or adjuvant chemoradiotherapy in the ARTIST trial [76].…”

Section: Msi and Effect Of Cytotoxic Agents: Clinical Datamentioning

confidence: 95%

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Velzen

Derks

Grieken

et al. 2020

Cancer Treatment Reviews

116

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Gastroesophageal cancers are a major cause of death worldwide and treatment outcomes remain poor. Adequate predictive biomarkers have not been identified. Microsatellite instability (MSI) as a result of mismatch repair deficiency is present in four to twenty percent of gastroesophageal cancers and has been associated with favorable survival outcomes compared to microsatellite stable tumors. This prognostic advantage may be related to immunosurveillance, which may also explain the favorable response to immune checkpoint inhibition observed in MSI high (MSI-H) tumors. The value of conventional cytotoxic treatment in MSI-H tumors is unclear and results on its efficacy range from detrimental to beneficial effects. Here the recent data on MSI as a predictive factor for outcome of gastroesophageal cancer treatment is reviewed.

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“…Adjuvant chemotherapy was associated with enhanced DFS time in patients exhibiting microsatellite stability, but it was not associated with any benefit in patients with high MSI (35). The post hoc analyses from the ARTIST trial in Asian patients also found that MSI-high status was associated with improved survival outcomes in patients with GC compared with MSI-low status (36). However, a separate retrospective analysis of 429 patients reported that adjuvant chemoradiotherapy was associated with notably improvements in the OS times of patients with stage III GC, respective of MSI status (37).…”

Section: Microsatellite Instability (Msi)mentioning

confidence: 96%

Challenges surrounding postoperative adjuvant chemotherapy for T2N0 gastric cancer (Review)

Sun

Wang

2020

Oncol Lett

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Determining the requirement for adjuvant chemotherapy in patients with stage IB gastric cancer (GC), and particularly for those with stage T2N0 (muscularis propria) disease, remains challenging. Patients with stage II/III disease benefit from postoperative adjuvant therapy; however, the randomized trials examining whether such therapy affords any survival benefit to patients with T2N0 disease are not sufficient. Current evidence suggests that not all patients with T2N0 disease should undergo such treatment, but only those with a high risk. To date, a number of retrospective studies have attempted to identify factors that are predictive of increased risk in an effort to guide adjuvant therapy-related clinical decision making. The National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology have published guidelines regarding factors associated with increased patient risk. As a result, treatment decisions for patients with stage T2N0 disease are currently determined on an individualized basis, in light of risk factors and the potential benefits of treatment. The present review surveyed current evidence related to the treatment of patients with high-risk GC and highlighted the potential avenues for future investigated. Contents

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Prognostic Impact of Microsatellite Instability in Asian Gastric Cancer Patients Enrolled in the ARTIST Trial

Cited by 34 publications

References 13 publications

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

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

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Challenges surrounding postoperative adjuvant chemotherapy for T2N0 gastric cancer (Review)

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