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Annamaria Catino



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-53 - Bone Metastases and Efficacy of Immunotherapy in Patients with Pretreated Advanced Non-Small-Cell Lung Cancer (NSCLC) (ID 11980)

      16:45 - 18:00  |  Author(s): Annamaria Catino

      • Abstract

      Background

      Approximately 40% of NSCLC patients develop bone metastases (BoM). Bone has active functions in regulating immune system. To date, no trial evaluated the role of BoM in modulating response to immunotherapy. Aim of the present study was to investigate whether presence of BoM impact on immunotherapy efficacy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Two different cohorts of pretreated NSCLC patients (cohort A: Non-squamous; cohort B: Squamous) were evaluated for nivolumab efficacy in terms of objective response rate (ORR), progression free survival (PFS), and overall survival (OS) according to presence or absence of BoM. All patients received nivolumab at standard dose of 3 mg/kg every 2 weeks within the Italian Expanded Access Program.

      4c3880bb027f159e801041b1021e88e8 Result

      Cohort A accounted for 1588 patients with non-squamous NSCLC: 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 370 patients with squamous histology: 102 BoM+ (32%) and 251 BoM- (68%). In Cohort A, BoM+ had a significantly lower ORR (12% versus 34%; p < 0.0001), shorter PFS (2.0 versus 4.0 months, p < 0.0001) and shorter OS (7.4 versus 15.3 months, p <0.0001). In cohort B, BoM+ had significantly lower ORR (15% versus 22%; p < 0.04), shorter PFS (2.7 versus 5.4 months, p <0.0001) and shorter OS (5.0 versus 10.9 months, p <0.0001). Presence of BoM negatively affected outcome irrespective of PS (OS cohort A: PS-0 BoM+ 12.0 versus 20.9 months in PS-0 BoM-, p<0.0001; OS cohort B: PS-0 BoM+ 5.8 versus 16.4 months in PS-0 BoM-, p<0.0001). Multivariate analysis confirmed that presence of BoM independently associated with higher risk of death with HR 1.64 and HR 1.78, for Cohort A and B, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results, the first assessing BoM in patients treated with immunotherapy, suggested that BoM predict lower efficacy of immunotherapy. BoM should be included as stratification factor in clinical trials.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-21 - Women with Synchronous or Metachronous Lung and Ovarian Cancers: A Multi-Institutional Report (ID 12485)

      16:45 - 18:00  |  Author(s): Annamaria Catino

      • Abstract
      • Slides

      Background

      In women, lung cancer (LC) and ovarian cancer (OC) are, respectively, the second and eighth malignancies for incidence in developed Countries. Despite increasing incidence and mortality of LC, association with OC is rare and no literature data are available on this topic yet. Our aim was to describe a series of patients with synchronous or metachronous LC and OC and to identify common clinical and pathological patterns.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrieved the medical charts of patients who referred to 30 European Oncological Institutes from 2008 to 2018. When patients with synchronous (up to 3 months of time interval in onset) or metachronous LC and OC were found, we collected detailed medical history, pathological features and clinical outcomes. Whenever available, formalin fixed paraffin embedded tumor tissue from both specimens was collected for centralized pathology revision with an immunohistochemical marker panel including TTF-1 and PAX-8. In ambiguous cases, a broader panel was performed (p40, CK-7, WT1, CA125, Calretinin, EMA, CEA, CgA, Vimentin, Napsin-A). Whenever tested, genetic alterations in LC and OC were also reported.

      4c3880bb027f159e801041b1021e88e8 Result

      As of April 2018, among 30 European Oncological Centers (Italy, France, Slovenia), 11 retrieved in their series patients with a history of LC and OC, for a total of 18 cases in the last 10 years. Paired histological specimens were available in 6 cases. One patient was excluded, since pathology revision revealed that lung lesions were metastases from serous OC. Thus, analyses were performed on 17 patients. In 10/17 cases (58.8%), LC and OC were metachronous and, in 6/10 cases, OC preceded LC diagnosis, with a median interval of 4.5 years. Median age at diagnosis of the first malignancy was 62 years, the majority of patients (64.7%) were never-smoker, 6 had cancer familial history. Interestingly, 4 patients (23.5%) reported also a third or fourth malignancy. After a median follow-up of 6.5 years, 10 patients are alive. Regarding histology, most of LC were adenocarcinoma (14/17, 82.3%). Molecular status was available in 9/14 cases: 4 had EGFR mutation, 1 B-RAF mutation and 2 ALK translocation. OC were mostly high-grade serous (83,3%). BRCA status was available in 6 patients: 2 mutated, 2 wild-type and 2 affected by variants of unknown significance (USV). Moreover, one synchronous case presented both BRCA-USV and B-RAF mutation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our series, synchronous and metachronous LC and OC were often driven by genetic alterations. Further genetic analysis with next generation sequencing technology has already been planned.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-12 - Prognostic and Predictive Role of Peripheral Blood Biomarkers in NSCLC Patients Treated with Checkpoint, a Single-Center Experience. (ID 14004)

      12:00 - 13:30  |  Author(s): Annamaria Catino

      • Abstract
      • Slides

      Background

      Tumor characteristics and host immune system play a crucial role for the immune response. As reported in preclinical studies, a sustain immune cell proliferation in the periphery is necessary for the immune response and tumor destruction. More evidence in melanoma patients (pts) and less evidence are available in non small cell lung cancer (NSCLC). Aim of this study is to demonstrate the role of the peripheral blood as biomarkers in NSCLC patients treated with checkpoint inhibitors (CPIs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      94 evaluable patients from one institution NSCLC pts, treated with at least one course immunotherapy (IO) (nivolumab and pembrolizumab) in 2nd or further line, were considered for analysis. Baseline peripheral blood, at week 2 and 4 were collected for each patients. Univariate analysis were performed and correlation between biomarkers and progression free-survival (PFS) and overall survival (OS) are reported.

      4c3880bb027f159e801041b1021e88e8 Result

      median age was 67 years (31-86 years), most pts were male (80%), 35 pts were S and 59 NS. 75,5% of pts were smokers and Eastern Cooperative Oncology Group (ECOG) pre-IO were: 0 (5,3%), 1 (58,5%) and 2 (36,2%). Overall median (m) PFS and mOS were 3,93 months (mo) and 20,7 mo respectively. Baseline absolute neutrophil count (ANC) ≥ 7500/µL and neutrophil to lymphocyte ratio (NLR) >5 correlate with worse PFS (3.3 mo vs 5.5 mo, p=0.04 and 2.8 mo vs 5.4 mo, p=0.006 respectively) and OS ( 15.6 mo vs 34.9 mo p=0.02 and 16.7 vs 34.9 mo p=0.004, respectively ). Poor OS and PFS were persist at week 2 in pts with NLR ≥5 (HR=0.3, p<0.0001 for OS and PFS), this was not significant at week 4. Also, baseline derived neutrophil to lymphocyte ratio (dNLR) >3 correlate with worse PFS ( p=0.01) and OS (p=0.016). Absolute lymphocyte count (ALC) ≥1000/µL at baseline and week 2 confer higher PFS (5.3 mo vs 3.1 mo, p=0.05) and a tred in OS. Interestingly, week-4 absolute monocytic count (AMC)≥ 1000/µL imply a poor PFS and this was not observed at baseline and week 2. Low, absolute eosinophil count (AEC) <50/ µL correlate with worse PFS (p=0.031). Finally, pts with lymphocyte monocyte ratio (LMR)≥ 1.5 at baseline, week 2 and 4 correlate with better survival.

      Table. 1 Univariate analysis of peripheral blood biomarker and survival outcome in NSCLC patients treated with immunotherapy

      Biomarker

      Outcome

      Survival

      (months)

      Impact

      (HR CI95%, p-value)

      Results

      Baseline

      ANC≥ 7500/µL

      OS

      15.6 mo vs 34.9 mo

      HR= 0.43, p=0.002

      Poor OS

      Poor PFS

      PFS

      3.3 mo vs 5.5 mo

      HR= 0.61, p=0.04

      Baseline

      NLR ≥ 5

      OS

      16.7 mo vs 34.9 mo

      HR=0.45, p=0.004

      Poor OS

      Poor PFS

      PFS

      2.8 mo vs 5.4 mo

      HR=0.50, p=0.006

      2 weeks

      NLR≥ 5

      OS

      11.9 mo vs 35 mo

      HR=0.32, p<0.0001

      Poor OS

      Poor PFS

      PFS

      2.6 mo vs 6.1 mo

      HR=0.31, p<0.0001

      Baseline

      dNLR> 3

      OS

      16.7 mo vs 34.8 mo

      HR= 0.51, p=0.016

      Poor OS

      Poor PFS

      PFS

      2.8 mo vs 5.4 mo

      HR= 0.52, p= 0.01

      Baseline

      ALC≥ 1000/µL

      OS

      31.7 mo vs 26.4 mo

      HR=1.23, p=0.54

      Same OS

      Good PFS

      PFS

      5.3 mo vs 3.1 mo

      HR= 1.8, p=0.05

      2 weeks

      ALC≥ 1000/µL

      OS

      34.8 vs 18 mo

      HR=1.4, p=0.14

      Same OS

      Good PFS

      PFS

      8.1 mo vs 3.3 mo

      HR=1.8 , p=0.007

      4 weeks

      AMC≥ 1000/ µL

      OS

      34.8 mo vs 31.7 mo

      HR=1.0, p=0.91

      Same OS

      Poor PFS

      PFS

      3.3 mo vs 8.0 mo

      HR=0.43, p=0.003

      Baseline

      LMR≥ 1.5

      OS

      34.8 mo vs 15.0 mo

      HR=2.1, p=0.007

      Good OS

      Good PFS

      PFS

      5.3 mo vs 2.6 mo

      HR=1.8, p=0.025

      2 weeks

      LMR≥ 1.5

      OS

      34.9 mo vs 15.0 mo

      HR=1.92, p=0.025

      Good OS

      Good PFS

      PFS

      6.1 mo vs 2.8 mo

      HR=3.4, p<0.001

      4 weeks

      LMR≥ 1.5

      OS

      35.1 mo vs 16.7 mo

      HR=2.7, p=0.003

      Good OS

      Good PFS

      PFS

      5.9 mo vs 3 mo

      HR=2, p=0.017

      Baseline

      (AEC) <50/ µL

      OS

      26.4 mo vs 24.6 mo

      HR=0.83, p=0.55

      Same OS

      Poor PFS

      PFS

      3.4 mo vs 5.6 mo

      HR=0.55, p=0.034

      NSCLC non-small cell lung cancer, ALC absolute lymphocyte count, ANC absolute neutrophil count, NLR neutrophil to lymphocyte ratio, dNLR absolute neutrophil count/(white blood cell count-absolute neutrophil count), AEC absolute eosinophil count, AMC absolute monocyte count, LMR lymphocyte monocyte count, OS overall survival, PFS progression free survival, RR response rate, HR hazard ratio,

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite the retrospective nature, in our knowledge, this is the first study to demonstrate the role of AMC in NSCLC pts. Also, LMR could probably reflect the peripheral immune-fitness. However, prospective sudies are needed to confirm their role.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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