Circulating miRNAs and PD-L1 tumor expression are associated with survival in advanced NSCLC patients treated with immunotherapy: A prospective study

Mattia Boeri, Massimo Milione, Claudia Proto, Diego Signorelli, Giuseppe Lo Russo, Carlotta Galeone, Carla Verri, Mavis Mensah, Giovanni Centonze, Antonia Martinetti, Elisa Sottotetti, Ugo Pastorino, Marina Chiara Garassino, Gabriella Sozzi

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Purpose: Immune-checkpoint inhibitors (ICI) have improved the survival of patients with non–small cell lung cancer (NSCLC). However, only a subset of patients benefit from ICIs, and the role of PD-L1 as predictive biomarker is still debated. A plasma immune-related miRNA-signature classifier (MSC) was established in lung cancer screening settings to identify the lethal form of the disease in early stages. In this exploratory study, we tested the efficacy of the MSC as prognostic marker in patients with advanced NSCLC treated with ICIs. Experimental Design: The MSC risk level was prospectively assessed in a consecutive series of 140 patients with NSCLC before starting treatment with ICIs. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in strata of PD-L1 and MSC alone or combined were considered as endpoints. Multiple plasma samples to monitor MSC risk level during treatment were also profiled. Results: Adequate tissue and plasma samples were available from 111 (79%) and 104 (75%) patients with NSCLC, respectively. MSC risk level was associated with ORR (P ¼ 0.0009), PFS [multivariate HR ¼ 0.31; 95% confidence interval (CI), 0.17–0.56; P ¼ 0.0001], and OS (multivariate HR ¼ 0.33; 95% CI, 0.18–0.59; P ¼ 0.0002). The combination of MSC and PD-L1 stratified patients into three risk groups having 39%–18%–0% 1-year PFS (P < 0.0001) and 88%–44%–0% 1-year OS (P < 0.0001), according to the presence of 2–1–0 favorable markers. During treatment, MSC risk level decreased or remained low until tumor progression in patients with responsive or stable disease. Conclusions: The plasma MSC test could supplement PD-L1 tumor expression to identify a subgroup of patients with advanced lung cancer with worse ORR, PFS, and OS in immunotherapy regimens.

Original languageEnglish
Pages (from-to)2166-2173
Number of pages8
JournalClinical Cancer Research
Volume25
Issue number7
DOIs
Publication statusPublished - Apr 1 2019

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MicroRNAs
Non-Small Cell Lung Carcinoma
Immunotherapy
Prospective Studies
Survival
Neoplasms
Disease-Free Survival
Lung Neoplasms
Confidence Intervals
Early Detection of Cancer
Research Design
Therapeutics
Biomarkers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Circulating miRNAs and PD-L1 tumor expression are associated with survival in advanced NSCLC patients treated with immunotherapy : A prospective study. / Boeri, Mattia; Milione, Massimo; Proto, Claudia; Signorelli, Diego; Russo, Giuseppe Lo; Galeone, Carlotta; Verri, Carla; Mensah, Mavis; Centonze, Giovanni; Martinetti, Antonia; Sottotetti, Elisa; Pastorino, Ugo; Garassino, Marina Chiara; Sozzi, Gabriella.

In: Clinical Cancer Research, Vol. 25, No. 7, 01.04.2019, p. 2166-2173.

Research output: Contribution to journalReview article

Boeri, Mattia ; Milione, Massimo ; Proto, Claudia ; Signorelli, Diego ; Russo, Giuseppe Lo ; Galeone, Carlotta ; Verri, Carla ; Mensah, Mavis ; Centonze, Giovanni ; Martinetti, Antonia ; Sottotetti, Elisa ; Pastorino, Ugo ; Garassino, Marina Chiara ; Sozzi, Gabriella. / Circulating miRNAs and PD-L1 tumor expression are associated with survival in advanced NSCLC patients treated with immunotherapy : A prospective study. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 7. pp. 2166-2173.
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title = "Circulating miRNAs and PD-L1 tumor expression are associated with survival in advanced NSCLC patients treated with immunotherapy: A prospective study",
abstract = "Purpose: Immune-checkpoint inhibitors (ICI) have improved the survival of patients with non–small cell lung cancer (NSCLC). However, only a subset of patients benefit from ICIs, and the role of PD-L1 as predictive biomarker is still debated. A plasma immune-related miRNA-signature classifier (MSC) was established in lung cancer screening settings to identify the lethal form of the disease in early stages. In this exploratory study, we tested the efficacy of the MSC as prognostic marker in patients with advanced NSCLC treated with ICIs. Experimental Design: The MSC risk level was prospectively assessed in a consecutive series of 140 patients with NSCLC before starting treatment with ICIs. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in strata of PD-L1 and MSC alone or combined were considered as endpoints. Multiple plasma samples to monitor MSC risk level during treatment were also profiled. Results: Adequate tissue and plasma samples were available from 111 (79{\%}) and 104 (75{\%}) patients with NSCLC, respectively. MSC risk level was associated with ORR (P ¼ 0.0009), PFS [multivariate HR ¼ 0.31; 95{\%} confidence interval (CI), 0.17–0.56; P ¼ 0.0001], and OS (multivariate HR ¼ 0.33; 95{\%} CI, 0.18–0.59; P ¼ 0.0002). The combination of MSC and PD-L1 stratified patients into three risk groups having 39{\%}–18{\%}–0{\%} 1-year PFS (P < 0.0001) and 88{\%}–44{\%}–0{\%} 1-year OS (P < 0.0001), according to the presence of 2–1–0 favorable markers. During treatment, MSC risk level decreased or remained low until tumor progression in patients with responsive or stable disease. Conclusions: The plasma MSC test could supplement PD-L1 tumor expression to identify a subgroup of patients with advanced lung cancer with worse ORR, PFS, and OS in immunotherapy regimens.",
author = "Mattia Boeri and Massimo Milione and Claudia Proto and Diego Signorelli and Russo, {Giuseppe Lo} and Carlotta Galeone and Carla Verri and Mavis Mensah and Giovanni Centonze and Antonia Martinetti and Elisa Sottotetti and Ugo Pastorino and Garassino, {Marina Chiara} and Gabriella Sozzi",
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TY - JOUR

T1 - Circulating miRNAs and PD-L1 tumor expression are associated with survival in advanced NSCLC patients treated with immunotherapy

T2 - A prospective study

AU - Boeri, Mattia

AU - Milione, Massimo

AU - Proto, Claudia

AU - Signorelli, Diego

AU - Russo, Giuseppe Lo

AU - Galeone, Carlotta

AU - Verri, Carla

AU - Mensah, Mavis

AU - Centonze, Giovanni

AU - Martinetti, Antonia

AU - Sottotetti, Elisa

AU - Pastorino, Ugo

AU - Garassino, Marina Chiara

AU - Sozzi, Gabriella

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Purpose: Immune-checkpoint inhibitors (ICI) have improved the survival of patients with non–small cell lung cancer (NSCLC). However, only a subset of patients benefit from ICIs, and the role of PD-L1 as predictive biomarker is still debated. A plasma immune-related miRNA-signature classifier (MSC) was established in lung cancer screening settings to identify the lethal form of the disease in early stages. In this exploratory study, we tested the efficacy of the MSC as prognostic marker in patients with advanced NSCLC treated with ICIs. Experimental Design: The MSC risk level was prospectively assessed in a consecutive series of 140 patients with NSCLC before starting treatment with ICIs. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in strata of PD-L1 and MSC alone or combined were considered as endpoints. Multiple plasma samples to monitor MSC risk level during treatment were also profiled. Results: Adequate tissue and plasma samples were available from 111 (79%) and 104 (75%) patients with NSCLC, respectively. MSC risk level was associated with ORR (P ¼ 0.0009), PFS [multivariate HR ¼ 0.31; 95% confidence interval (CI), 0.17–0.56; P ¼ 0.0001], and OS (multivariate HR ¼ 0.33; 95% CI, 0.18–0.59; P ¼ 0.0002). The combination of MSC and PD-L1 stratified patients into three risk groups having 39%–18%–0% 1-year PFS (P < 0.0001) and 88%–44%–0% 1-year OS (P < 0.0001), according to the presence of 2–1–0 favorable markers. During treatment, MSC risk level decreased or remained low until tumor progression in patients with responsive or stable disease. Conclusions: The plasma MSC test could supplement PD-L1 tumor expression to identify a subgroup of patients with advanced lung cancer with worse ORR, PFS, and OS in immunotherapy regimens.

AB - Purpose: Immune-checkpoint inhibitors (ICI) have improved the survival of patients with non–small cell lung cancer (NSCLC). However, only a subset of patients benefit from ICIs, and the role of PD-L1 as predictive biomarker is still debated. A plasma immune-related miRNA-signature classifier (MSC) was established in lung cancer screening settings to identify the lethal form of the disease in early stages. In this exploratory study, we tested the efficacy of the MSC as prognostic marker in patients with advanced NSCLC treated with ICIs. Experimental Design: The MSC risk level was prospectively assessed in a consecutive series of 140 patients with NSCLC before starting treatment with ICIs. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in strata of PD-L1 and MSC alone or combined were considered as endpoints. Multiple plasma samples to monitor MSC risk level during treatment were also profiled. Results: Adequate tissue and plasma samples were available from 111 (79%) and 104 (75%) patients with NSCLC, respectively. MSC risk level was associated with ORR (P ¼ 0.0009), PFS [multivariate HR ¼ 0.31; 95% confidence interval (CI), 0.17–0.56; P ¼ 0.0001], and OS (multivariate HR ¼ 0.33; 95% CI, 0.18–0.59; P ¼ 0.0002). The combination of MSC and PD-L1 stratified patients into three risk groups having 39%–18%–0% 1-year PFS (P < 0.0001) and 88%–44%–0% 1-year OS (P < 0.0001), according to the presence of 2–1–0 favorable markers. During treatment, MSC risk level decreased or remained low until tumor progression in patients with responsive or stable disease. Conclusions: The plasma MSC test could supplement PD-L1 tumor expression to identify a subgroup of patients with advanced lung cancer with worse ORR, PFS, and OS in immunotherapy regimens.

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U2 - 10.1158/1078-0432.CCR-18-1981

DO - 10.1158/1078-0432.CCR-18-1981

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