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Luis Cabezon-Gutierrez



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-07 - Definitive Results of a Clinical and Molecular Multicentric Characterization of Long-Term Survivors with Advanced Non-Small Cell Lung Cancer  (Now Available) (ID 1191)

      08:00 - 18:00  |  Author(s): Luis Cabezon-Gutierrez

      • Abstract
      • Slides

      Background

      Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid.

      Method

      In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples.

      Result

      Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047)

      Conclusion

      We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-98 - Neutrophil-Platelet Score (NPS), a Predictive Systemic Inflammation Score for Pembrolizumab in First Line of Advanced NSCLC Patients (ID 2711)

      10:15 - 18:15  |  Author(s): Luis Cabezon-Gutierrez

      • Abstract

      Background

      Systemic inflammation response can be characterized by changes of peripheral blood cell amounts. Several blood cell-based scores have been found to have prognostic value in some tumors treated with ICI. Neutrophil-platelet score (NPS) is a systemic inflammation-based score characterizing 3 prognostic groups: good (0), neutrophils <=7500 and platelets <=400000; intermediate (1), neutrophils >7500 or platelets >400000; poor (2), neutrophils >7500 and platelets >400000). It has never been evaluated as prognostic biomarker in first line treatment setting of non-small-cell lung cancer (NSCLC) patients treated with pembrolizumab.

      Method

      This is a multicenter retrospective study with the aim to evaluate prognostic value of NPS in patients with advanced NSCLC and high PD-L1 expression treated with pembrolizumab monotherapy between September 2016 and March 2019. Clinical data were contributed by 12 medical centers in Spain. Primary endpoint was association of NPS with overall survival (OS).

      Result

      121 patients were evaluated. Median age was 68 years (38-88). 90 (74,4%) were male and 90 (74,4%) had PS1. Predominant histologies were adenocarcinoma (68,6%) and squamous-cell carcinoma (23,1%). Median number of cycles was 7 (1-33). Median follow-up: 6,5 months. Most were current or former smokers (95,9%). Only 1 patient had driver mutation (ALK rearrangement). 66,9% had 2 or more metastatic locations, 18,2% had central nervous system (CNS) disease, 17,4% liver metastasis, and 41,3% bone metastasis. Response rate was 40,4% according to RECISTv1.1 criteria. 11% had hyperprogression and 7,2% pseudoprogression. Estimated 12-month-OS was 62% (95%CI: 49.1%-72.5%) and estimated 12-month-PFS was 44.2% (95%CI: 31.1%-56.5%). Higher NPS was associated with poor PFS: NPS1 HR 1,23 (95%CI, 0,61-2,46), p=0,56; NPS2 HR 3,56 (95%CI, 1,61-7,86), p=0,002. NPS was not associated with disease control rate (DCR) or overall response rate (ORR).

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      Conclusion

      NPS predicted OS and PFS in advanced NSCLC patients with high PD-L1 expression treated with first line pembrolizumab monotherapy. NPS2 subgroup has an especially bad prognosis in spite of high PD-L1 expression and frontline treatment with pembrolizumab. These results need to be validated in prospective studies.