Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab

Carlo Genova, Simona Boccardo, Marco Mora, Erika Rijavec, Federica Biello, Giovanni Rossi, Marco Tagliamento, Maria Giovanna Dal Bello, Simona Coco, Angela Alama, Irene Vanni, Giulia Barletta, Rita Bianchi, Claudia Maggioni, Paolo Bruzzi, Francesco Grossi

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Abstract

Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS; 1.7 vs. 2.0 months; p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months; p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28; p = 0.021) and OS (HR = 2.38; p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research.

Original languageEnglish
JournalJournal of Clinical Medicine
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

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Non-Small Cell Lung Carcinoma
Survival
Drug Therapy
Platinum
Disease-Free Survival
Multivariate Analysis
Immunohistochemistry
nivolumab
Research
Population

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Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab. / Genova, Carlo; Boccardo, Simona; Mora, Marco; Rijavec, Erika; Biello, Federica; Rossi, Giovanni; Tagliamento, Marco; Dal Bello, Maria Giovanna; Coco, Simona; Alama, Angela; Vanni, Irene; Barletta, Giulia; Bianchi, Rita; Maggioni, Claudia; Bruzzi, Paolo; Grossi, Francesco.

In: Journal of Clinical Medicine, Vol. 8, No. 10, 01.10.2019.

Research output: Contribution to journalArticle

Genova, C, Boccardo, S, Mora, M, Rijavec, E, Biello, F, Rossi, G, Tagliamento, M, Dal Bello, MG, Coco, S, Alama, A, Vanni, I, Barletta, G, Bianchi, R, Maggioni, C, Bruzzi, P & Grossi, F 2019, 'Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab', Journal of Clinical Medicine, vol. 8, no. 10. https://doi.org/10.3390/jcm8101566
Genova, Carlo ; Boccardo, Simona ; Mora, Marco ; Rijavec, Erika ; Biello, Federica ; Rossi, Giovanni ; Tagliamento, Marco ; Dal Bello, Maria Giovanna ; Coco, Simona ; Alama, Angela ; Vanni, Irene ; Barletta, Giulia ; Bianchi, Rita ; Maggioni, Claudia ; Bruzzi, Paolo ; Grossi, Francesco. / Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab. In: Journal of Clinical Medicine. 2019 ; Vol. 8, No. 10.
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AU - Genova, Carlo

AU - Boccardo, Simona

AU - Mora, Marco

AU - Rijavec, Erika

AU - Biello, Federica

AU - Rossi, Giovanni

AU - Tagliamento, Marco

AU - Dal Bello, Maria Giovanna

AU - Coco, Simona

AU - Alama, Angela

AU - Vanni, Irene

AU - Barletta, Giulia

AU - Bianchi, Rita

AU - Maggioni, Claudia

AU - Bruzzi, Paolo

AU - Grossi, Francesco

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N2 - Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS; 1.7 vs. 2.0 months; p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months; p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28; p = 0.021) and OS (HR = 2.38; p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research.

AB - Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS; 1.7 vs. 2.0 months; p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months; p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28; p = 0.021) and OS (HR = 2.38; p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research.

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