• 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, Marin... more a Chiara Garassino, and Gabriella Sozzi. less
• Unit of Tumor Genomics, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. mattia.boeri@istitutotumori.mi.it.
• Clin Cancer Res. 2019 Apr 1; 25 (7): 2166-2173.

PurposeImmune-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 DesignThe 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.ResultsAdequate tissue and plasma samples were available from 111 (79%) and 104 (75%) patients with NSCLC, respectively. MSC risk level was associated with ORR (P = 0.0009), PFS [multivariate HR = 0.31; 95% confidence interval (CI), 0.17-0.56; P = 0.0001], and OS (multivariate HR = 0.33; 95% CI, 0.18-0.59; P = 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.ConclusionsThe 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.©2019 American Association for Cancer Research.

33 keywords...

hide…