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

Purpose: Immune-checkpoint inhibitors (ICIs) have improved the survival of NSCLC patients. 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 microRNA-signature classifier (MSC) was established in lung cancer screening settings in order to identify the lethal form of the disease in early stages. In the present exploratory study, we tested the efficacy of the MSC as prognostic marker in advanced NSCLC patients treated with ICIs. Experimental Design: The MSC risk level was prospectively assessed in a consecutive series of 140 NSCLC patients before starting treatment with ICIs. Overall response rate (ORR), progression-free (PFS) and overall survival (OS) in strata of PD-L1 and MSC alone or combined were considered as end-points. 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%) NSCLC patients, respectively. MSC risk level was associated with ORR (P=0.0009), PFS (multivariate HR=0.31; 95%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% one-year PFS (P<0.0001) and 88%-44%-0% one-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 advanced lung cancer patients with worse ORR, PFS and OS in immunotherapy regimens.

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