Maria Di Bartolomeo 1 , Federica Morano 1 , Alessandra Raimondi 1 , Rosalba Miceli 2 , Salvatore Corallo 1 , Elena Tamborini 3 , Federica Perrone 3 , Maria Antista 1 , Monica Niger 1 , Alessandro Pellegrinelli 3 , Giovanni Randon 1 , Filippo Pagani 1 , Antonia Martinetti 1 , Giovanni Fucà 1 , Filippo Pietrantonio 1,4 Show Affiliations »
Abstract
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BACKGROUND: Patients with high microsatellite instability (MSI) gastric cancer (GC ) show improved survival and no benefit or harm from adjuvant and/or perioperative chemotherapy. The role of immune microenvironment in GC is largely unknown. MATERIALS AND METHODS: In the present study, 256 tumor tissue blocks were centrally collected from patients enrolled in ITACA-S , a randomized adjuvant trial of 5-FU/LV versus sequential FOLFIRI and cisplatin-docetaxel . MSI status was assessed by multiplex PCR, inflammatory reaction by H&E morphological assessment, and programmed death-ligand 1 (PD-L1) expression by immunohistochemistry. RESULTS: Overall, 9% patients had MSI-high tumors, 23% had high inflammatory reaction , 11% had tumor PD-L1 ≥ 1%, and 11% had stromal PD-L1 ≥ 1%. A significant association with disease-free survival (DFS) and overall survival (OS ) was found for MSI-high (hazard ratio [HR], 0.43; p = .02; HR, 0.40; p = .02) and high inflammatory reaction (HR, 0.55; p = .010; HR, 0.53; p = .008) but not for PD-L1. At multivariable analysis, only MSI showed an independent association with both DFS (p = .02) and OS (p = .01), whereas inflammatory reaction showed an independent association only with OS (p = .04). Patients with tumor PD-L1 ≥ 1% had a significantly longer DFS in sequential chemotherapy than in than 5-FU/LV arm (interaction p = .04) and a trend for OS (interaction p = .12). CONCLUSION: Our data suggest that MSI status could be a useful prognostic biomarker in patients with radically resected stage II-III GC and should be used as stratification factor in future trials. Tumor PD-L1 ≥ 1% should be further investigated as a potential predictor of benefit from intensive chemotherapy. IMPLICATIONS FOR PRACTICE: In this post hoc analysis of patients with radically resected gastric cancer randomized to an intensive sequential chemotherapy regimen versus 5-FU/LV monotherapy as adjuvant treatment in the ITACA-S trial, MSI-high status was independently associated with better disease-free survival and overall survival (OS) and inflammatory reaction was independently associated with better OS. Moreover, tumor PD-L1 expression ≥1% was associated with greater benefit from intensive sequential chemotherapy compared with 5-fluorouracil plus leucovorin (5-FU/LV ), whereas PD-L1 expression <1% was not, conditioning a statistically significant interaction between such biomarker and treatment arms. The meta-analysis of individual patients' data from available studies could yield data on the role of MSI status that could inform clinical decisions. © AlphaMed Press 2019.
RCT Entities: Population
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BACKGROUND: Patients with high microsatellite instability (MSI) gastric cancer (GC ) show improved survival and no benefit or harm from adjuvant and/or perioperative chemotherapy. The role of immune microenvironment in GC is largely unknown. MATERIALS AND METHODS: In the present study, 256 tumor tissue blocks were centrally collected from patients enrolled in ITACA-S, a randomized adjuvant trial of 5-FU /LV versus sequential FOLFIRI and cisplatin -docetaxel . MSI status was assessed by multiplex PCR, inflammatory reaction by H&E morphological assessment, and programmed death-ligand 1 (PD-L1 ) expression by immunohistochemistry. RESULTS: Overall, 9% patients had MSI-high tumors, 23% had high inflammatory reaction, 11% had tumor PD-L1 ≥ 1%, and 11% had stromal PD-L1 ≥ 1%. A significant association with disease-free survival (DFS) and overall survival (OS ) was found for MSI-high (hazard ratio [HR], 0.43; p = .02; HR, 0.40; p = .02) and high inflammatory reaction (HR, 0.55; p = .010; HR, 0.53; p = .008) but not for PD-L1 . At multivariable analysis, only MSI showed an independent association with both DFS (p = .02) and OS (p = .01), whereas inflammatory reaction showed an independent association only with OS (p = .04). Patients with tumor PD-L1 ≥ 1% had a significantly longer DFS in sequential chemotherapy than in than 5-FU /LV arm (interaction p = .04) and a trend for OS (interaction p = .12). CONCLUSION: Our data suggest that MSI status could be a useful prognostic biomarker in patients with radically resected stage II-III GC and should be used as stratification factor in future trials. Tumor PD-L1 ≥ 1% should be further investigated as a potential predictor of benefit from intensive chemotherapy. IMPLICATIONS FOR PRACTICE: In this post hoc analysis of patients with radically resected gastric cancer randomized to an intensive sequential chemotherapy regimen versus 5-FU /LV monotherapy as adjuvant treatment in the ITACA-S trial, MSI-high status was independently associated with better disease-free survival and overall survival (OS ) and inflammatory reaction was independently associated with better OS . Moreover, tumor PD-L1 expression ≥1% was associated with greater benefit from intensive sequential chemotherapy compared with 5-fluorouracil plus leucovorin (5-FU /LV ), whereas PD-L1 expression <1% was not, conditioning a statistically significant interaction between such biomarker and treatment arms. The meta-analysis of individual patients ' data from available studies could yield data on the role of MSI status that could inform clinical decisions. © AlphaMed Press 2019.
Entities: Chemical
Disease
Gene
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Keywords:
Adjuvant chemotherapy; Biomarkers; Gastric cancer; Microsatellite instability; PD-L1
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Year: 2019
PMID： 32162808 PMCID： PMC7066701 DOI： 10.1634/theoncologist.2019-0471
Source DB: PubMed Journal: Oncologist ISSN： 1083-7159