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NADIM: Risk of progression identified through RNA sequencing

Presented by
Ms Marta Casarrubios, Hospital Universitario Puerta de Hierro-Majadahonda, Spain
WCLC 2022
Phase 2, NADIM
In individuals who did not achieve complete pathological response (CPR) from the phase 2 NADIM trial, an immune expression signature was identified that was associated with disease progression [1]. According to the authors, these results could help in the follow-up and management of patients with resectable non-small cell lung cancer (NSCLC).

The phase 2 NADIM trial (NCT03081689) investigated the safety and efficacy of neoadjuvant chemotherapy plus nivolumab in 46 patients with stage IIIA, resectable NSCLC. The positive results of this trial were previously published in The Lancet Oncology [2]. Through RNA sequencing, the current analysis aimed to identify biomarkers of disease progression in patients that had received surgery in this trial (n=36). Ms Marta Casarrubios (Hospital Universitario Puerta de Hierro-Majadahonda, Spain) presented the findings.

The analysis identified 22 differentially expressed genes between patients achieving a CPR and those who did not achieve CPR. The majority of these genes were associated with proliferation and tumour marker genes and were upregulated in patients who did not achieve CPR. Furthermore, non-CPR tumours appeared to have a higher proportion of follicular T-helper cells (P=0.025), whereas CPR tumours showed upregulation of antigen processing, T-cell receptor co-expression, and lymphocyte infiltration pathways. In total, 10 genes were differentially upregulated in tumours from patients with disease progression, mostly being genes related to tumour markers or type 1 interferon signalling. Finally, in the non-CPR population, upregulation of AKT1 and a higher proportion of activated neutrophil dendritic cells were associated with a reduced progression-free and overall survival.

  1. Casarrubios M, et al. Tumor Bulk-RNA seq identifies patients at high risk of progression in non-complete pathological responders from NADIM trial. 03, WCLC 2022, Vienna, Austria, 06–09 August.
  2. Provencio M, et al. Lancet Oncology. 2020;21(11):1413-1422


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