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- Title
Prognostic and Predictive Value of Microsatellite Instability, Inflammatory Reaction and PD‐L1 in Gastric Cancer Patients Treated with Either Adjuvant 5‐FU/LV or Sequential FOLFIRI Followed by Cisplatin and Docetaxel: A Translational Analysis from the ITACA‐S Trial
- Authors
Di Bartolomeo, Maria; Morano, Federica; Raimondi, Alessandra; Miceli, Rosalba; Corallo, Salvatore; Tamborini, Elena; Perrone, Federica; Antista, Maria; Niger, Monica; Pellegrinelli, Alessandro; Randon, Giovanni; Pagani, Filippo; Martinetti, Antonia; Fucà, Giovanni; Pietrantonio, Filippo
- Abstract
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. This article reports a post‐hoc analysis of immune‐related biomarkers in patients with radically resected gastric cancer enrolled in the ITACA‐S trial.
- Subjects
CANCER patients; CISPLATIN; COMBINED modality therapy; DEGENERATION (Pathology); FLUOROURACIL; FOLINIC acid; IMMUNOHISTOCHEMISTRY; INFLAMMATION; MEMBRANE proteins; MULTIVARIATE analysis; GENETIC mutation; STATISTICS; STOMACH tumors; TUMOR markers; DOCETAXEL; DATA analysis; PREDICTIVE tests; IRINOTECAN
- Publication
Oncologist, 2020, Vol 25, Issue 3, pe460
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2019-0471