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María Sereno



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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  |  Presenting Author(s): María Sereno

      • 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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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-16 - Early Antibiotic Use Affects the Efficacy of First Line Immunotherapy in Lung Cancer Patients but Route of Administration Seems to be Decisive (ID 1155)

      09:45 - 18:00  |  Author(s): María Sereno

      • Abstract

      Background

      Several studies found that cancer patients treated with PD-1 immune checkpoint inhibitors (CKIs) who receive antibiotics (ATX) had worse efficacy outcomes because ATX can dysregulate gut microbiota. There are some data in pretreated non-small-cell lung cancer (NSCLC) and few data about the route of ATX administration, but it`s unkown whether ATX administration can also affect efficacy of CKIs in first line setting in patients treated with pembrolizumab monotherapy.

      Method

      This is a multicenter retrospective study. We included consecutive patients with advanced NSCLC with high PD-L1 expression (50%) treated with pembrolizumab monotherapy in first line, between September 2016 and March 2019, from 12 hospitals in Spain. The aim of the study was to evaluate if patients taking ATX 2 months before or within the first month after starting CKIs had worse OS, and if OS was affected by the route of administration and type of prescribed ATX.

      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. 45,5% received ATX, 65,5% of them intravenously and 34,5% orally. Most prescribed ABX were quinolones (40,7%) and penicillin or derivatives (35,2%). 21,5% received subsequent chemotherapy. 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%) Patients who received ABX had more risk of disease progression as best response (52,2% vs 24,5%,RR: 2.1, 95%CI: 1.2-3.7, p=0.007). Patients who received ATX had shorter OS (HR:1.9, 95%CI: 1.1-3.7, p=0.047) and shorter PFS (HR:2.6, 95%CI: 1.4-4.8, p=0.002). Patients who received ATX intravenously had shorter OS than those not treated (HR:2.8, 95%CI: 1.4-5.6) and than those who received ABX orally (HR:3.5, 95%CI: 1.2-10.3, p=.025) ). Patients treated with ABX also had shorter PFS than those not treated (HR: 3.5, 95%CI:1.8-6.8, p<0.001) and than those who received ABX orally (HR: 2.2, 95%CI:1-4.8, p=0.05). Similar HR were estimated adjusting by age, gender, stage, and hepatic and bone metastasis presence. There were no OS and PFS differences between patients who received ABX orally and those who did not received them. There were no survival differences according to type of ABX.

      Conclusion

      Our results suggest that use of intravenous ABX has a negative impact on disease control rate and survival outcomes (PFS and OS) in patients with naïve advanced NSCLC and high PD-L1 expression treated with pembrolizumab monotherapy in first line setting. Patients who received oral ABX had similar efficacy than those not treated with ABX. To our knowledge, this is the first retrospective study evaluating the impact of ATX on the efficacy of CKIs in first-line treatment setting of NSCLC patients.

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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): María Sereno

      • 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.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-33 - ctDNA Levels Significantly Predicts Survival in NSCLC Patients with an EGFR Activating Mutation (ID 2016)

      10:15 - 18:15  |  Author(s): María Sereno

      • Abstract

      Background

      Circulating tumor DNA (ctDNA) have been shown to be useful for non-invasive biomarker testing in non-small cell lung cancer (NSCLC). In addition, there is growing evidence supporting that ctDNA levels can be useful for tumor response to treatment monitoring. Nevertheless, data from large prospective clinical longitudinal studies still limited.

      Method

      300 plasma samples from 100 advanced NSCLC patients, with tumors harboring an EGFR activating mutation and treated with a first line tyrosine Kinase inhibitor were analyzed. Samples were collected before the start of treatment, at first follow up evaluation, at 7 month and at disease progression. ctDNA was analyzed by dPCR.

      Result

      Median follow up was 11.3 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, afatinib or gefitinib). Patients harboring a deletion in exon 19 or a mutation in exon 21 exhibited better survival than those with an insertion in exon 20 (P<0.001). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. ctDNA levels before the start of the treatment did not significantly predict survival, although a tendency was observed, with patients with high levels of ctDNA showing poorer outcome. On the contrary, patients in which the EGFR sensitizing mutation was undetectable at first follow up had a markedly better PFS and OS (HR=2.7; 95IC= 1.4-5.5 and HR= 5.5 95IC: 1.8-17 respectively). In the same way, patients in which the EGFR sensitizing mutation remained negative at 7months had a significantly increased PFS (HR: 2.8; 95IC: 1.2-6.6). None of the patients with undetectable levels at 7 months has deceased.

      Conclusion

      ctDNA levels is of prognostic significance in EGFR positive NSCLC patients with advance disease and can be useful to monitor treatment outcome

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    P2.05 - Interventional Diagnostic/Pulmonology (ID 168)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.05-10 - Liquid Biopsy: Association Between the Burden of Disease in Patients with EGFR-Mutated NSCLC and the Frequency of Its Detection in Blood (ID 2384)

      10:15 - 18:15  |  Author(s): María Sereno

      • Abstract
      • Slides

      Background

      In the management of patient’s whit non small cell lung cancer (NSCLC) with EGFR mutations after progression to first and second generation tyrosine kinasa inhibitors (TKI), the mechanism of resistance is very important. Our objective is to analyse the appearance kinetics of the T790M by means of digital PCR techniques in liquid biopsy.

      Method

      We conducted a multicenter study with 100 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyze the ctDNA by dPCR before the start of treatment, at first follow up evaluation, at 6 months and at disease progression.

      Result

      We included a total of 100 patients from July 2016 to December of 2017. Seven patients with Exon 20 insertion in EGFR were excluded (final sample 93). The median of follow-up was 12 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, gefitinib or afatinib). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. Of these cases, EGFR sensitizing mutation was detected in 75% of the patients with stage IVA and 85% in stage IVB respectively, p=0,075. The resistance mutation p.T790M was detected in 52% of the samples collected at disease progression. The probability to detect the resistance mutation p.T790M by liquid biopsy, is greater if the pre-treatment sample was positive for EGFR sensitizing mutation (11% vs 62%) p 0,009. In cases with progression of the disease the percent of detection of p.T790M was 52% and 54% in patients with Exon 19 deletion and L858R mutation respectively. The OS in patients with progression of the disease and p.T790M negative was 85% at 12 months (95%CI: 60%-94%) and 75% with p.T790M positive (95%CI: 49%-88%), p=0,01.

      Conclusion

      The burden of disease in patients with NSCLC mutated with EGFR is related to the appearance of sensitivity and resistance mutations in liquid biopsy. The probability to detect the resistance mutation p.T790M in blood, is greater if the pre-treatment sample was positive for EGFR sensitizing mutation.

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