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Hidehito Horinouchi



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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
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-51 - Efficacy Impact of Serum VEGF for Elderly or Poor PS Patients Receiving Anti-PD-1 Antibody with Advanced Non-Small Cell Lung Cancer (ID 1691)

      08:00 - 18:00  |  Author(s): Hidehito Horinouchi

      • Abstract
      • Slides

      Background

      Anti-programmed cell death (PD)-1 antibody therapies have shown durable clinical efficacy and manageable toxicity profiles, and have become a standard therapy in advanced non-small cell lung cancer (NSCLC). Because of manageable toxicity profiles, extensive interest in the potential benefits of anti-PD-1 antibody has expanded to high-risk patients such as the elderly or poor performance status (PS) patients. Here, we aimed to investigate predictive markers for the efficacy of anti-PD-1 antibody in elderly patients and poor PS patients.

      Method

      The medical records of 75≥ years old or PS2 NSCLC patients treated with anti-PD-1 antibody (e.g., nivolumab and pembrolizumab) at the National Cancer Center Japan between December 1, 2015, and May 31, 2018, were reviewed retrospectively. We evaluated the association between efficacy for anti-PD-1 antibody and gender, smoking status, histology, PD-ligand 1(PD-L1) expression on tumor cells, white blood cell counts, lymphocyte counts, albumin, lactate dehydrogenase, c-reactive protein, and serum vascular endothelial growth factor (VEGF). We divided patients into two groups with the median values.

      Result

      A total of 235 patients with advanced NSCLC treated with anti-PD-1 antibody were reviewed. Of these patients, 31 patients were ≥ 75 years old, and 22 patients were PS2. The median PFS was 6.9 months in patients aged ≥ 75 years and 2.1 months in PS2 patients. Cox proportional hazard regression analysis showed that only the low-VEGF was significantly associated with longer PFS in patients aged ≥ 75 years (HR, 0.35; 95% CI, 0.13-0.88; P = 0.025) and in PS2 patients (HR, 0.31; 95% CI, 0.10-0.85; P = 0.023). The overall response rate of patients with low-VEGF was tend to be higher than that with high-VEGF among patients aged ≥ 75 years (43% vs. 20%; P = 0.18) and PS2 patients (20% vs. 0%; P = 0.084).

      Conclusion

      Low-VEGF in patients aged ≥ 75 years and PS2 patients was associated with longer PFS. Serum VEGF may thus be a biomarker for the efficacy of anti-PD-1 antibody therapy.

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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.07 - Efficacy of Immune-Checkpoint Inhibitors and EGFR-TKIs in NSCLC Patients with High PD-L1 Expression (Now Available) (ID 667)

      14:00 - 15:30  |  Author(s): Hidehito Horinouchi

      • Abstract
      • Presentation
      • Slides

      Background

      Recently, several studies have demonstrated that patients with non-small cell lung carcinoma (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations show poor clinical outcomes in response to treatment with anti-programmed cell death-1 (PD-1) inhibitors. Conversely, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are not effective in NSCLC showing high programmed death ligand 1 (PD-L1) expression levels. In this study, we retrospectively investigated the relationship between high PD-L1 expression and the efficacy of PD-1 inhibitors and EGFR-TKIs in patients with NSCLC.

      Method

      The subjects of this study were patients with NSCLC who had received treatment with PD-1 inhibitors at the National Cancer Center Hospital between March 2017 and December 2018. The PD-L1 expression in the tumor cells was divided into two groups based on the tumor proportion score (TPS): <50% (low) and ≥50% (high).

      Result

      Of the 414 patients treated with PD-1 inhibitors, the 263 patients in whom the PD-L1 expression levels could be evaluated were considered as being eligible for inclusion in this study. Among the 153 patients with high PD-L1 expression, we assessed the efficacy of PD-1 inhibitors according to the EGFR mutation status. The objective response rate (ORR) was 29.4% (95% confidence interval [CI], 1.3 to 53.1) in the EGFR-mutated patients and 43.4% (95% CI, 35.4 to 51.8) in the EGFR wild-type patients. The median progression-free survival (PFS) was 5.3 months (95% CI, 1.3 to 12.4) in the EGFR-mutated patients and 8.3 months (95% CI, 6.0 to 11.7) in the EGFR wild-type patients (hazard Ratio [HR] = 0.62; 95% CI, 0.62 to 1.14). A total of 33 patients received EGFR-TKI therapy. We assessed the efficacy of EGFR-TKIs according to the PD-L1 expression level. The ORR was 50.0% (95% CI, 28.0 to 72.0) in the high PD-L1 expression group and 52.9% (95% CI, 31.0 to 73.8) in the low PD-L1 expression group. The median PFS was 18.8 months (95% CI, 2.8 to 35.7) in the high PD-L1 expression group and 12.7 months (95% CI, 7.2 to 20.9) in the low PD-L1 expression group (HR = 0.83; 95% CI, 0.38 to 1.81).

      PD-L1 High

      EGFR+

      PD-L1 High

      EGFR−

      PD-L1 Low

      EGFR+

      PD-L1 Low

      EGFR−

      Total N

      17

      136

      18

      92

      Median age, years (range)

      62 (47–85)

      62 (33–87)

      64.5 (37–83)

      62 (33–83)

      Sex (n)

      Female

      Male

      7

      10

      36

      100

      15

      3

      25

      67

      ECOG PS (n)

      0, 1

      2

      14

      3

      125

      11

      16

      2

      81

      11

      Smoking history (n)

      Never-smoker

      Smoker

      7

      10

      21

      115

      12

      6

      13

      79

      EGFR mutation status (n)

      Ex 19 del

      L858R

      Others

      7

      6

      4

      13

      2

      3

      ICI agent used (n)

      Pembrolizumab

      Nivolumab

      11

      6

      105

      31

      4

      14

      21

      71

      Line of ICI therapy (n)

      First-line

      Second-line

      Third-line or more

      2

      3

      12

      85

      42

      9

      5

      64

      23

      0

      2

      16

      Efficasy

      ORR (%)

      PD-1 inhibitors

      EGFR-TKIs

      PFS (months)

      PD-1 inhibitors

      EGFR-TKIs

      29.4

      50.0

      5.3

      18.8

      43.4

      8.3

      0

      52.9

      1.6

      12.7

      16.3

      3.8

      Conclusion

      Even in a population of NSCLC patients showing high PD-L1 expression, the efficacy of PD-1 inhibitors tended to be lower in the EGFR-mutated patients as compared to the EGFR wild-type patients. In regard to EGFR-mutated patients with a PD-L1 TPS of ≥50%, our findings suggested that high PD-L1 expression might not predict a poor efficacy of EGFR-TKIs.

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    MA15 - Usage of Computer and Molecular Analysis in Treatment Selection and Disease Prognostication (ID 141)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MA15.03 - Exploring Digital Pathology-Based Morphological Biomarkers for a Better Patients’ Selection to the Immune Checkpoint Inhibitor of Lung Cancer (Now Available) (ID 1777)

      15:45 - 17:15  |  Author(s): Hidehito Horinouchi

      • Abstract
      • Presentation
      • Slides

      Background

      For eligible patients’ selection for immune checkpoint inhibitor therapy (ICI), it is important to establish more accurate predicting biomarkers, in addition to PD-L1 IHC and MSI-high. We hypothesized that morphological characteristics should reflect genetic alteration, thus could predict ICI responsiveness. In this study, we examined the predictive potential of morphological characteristics using digital whole-slide images as a new biomarker for ICI-treatment on non-small cell lung cancer (NSCLC) and their relationship to PD-L1 IHC and genetic alterations.

      Method

      71 NSCLC who received ICI therapy were recruited. Digital images of H&E and PD-L1 (22C3) IHC stained slides of pre-treatment biopsied or resected materials were examined by previously reported image analysis techniques using e-Pathologist ® (NEC, Japan). Morphological characteristics of cancer cells (three and six parameters of nuclear shape and chromatin texture) were extracted as MC-scores. Of 11 cases (pilot cohort), PD-L1 IHC (22C3) and tumor mutation burden (TMB) by the NGS-based target sequence (NCC oncopanel ®) were examined. Correlation between MC-score, PD-L1 IHC, TMB status, and clinical outcome was calculated. A p-value of less than 0.05 was defined as statistically significant.

      Decision tree analysis for evaluating predicting ICI-responsiveness was built using statistically significant MC-scores. We also tested the predictive value of a deep learning analysis (AI model) with 5-fold cross-validation. AUC (area under the curve) of ROC analysis was calculated.

      Result

      Of the responders, the MC-score of cancer cell were statistically different from those of the non-responders; nuclear texture contour complexity (11.8 vs. 8.25, median value of responder vs. non-responders; p<0.01), homogeneity (0.396 vs. 0.421; p<0.01), angular second moment (ASM) (0.0203 vs. 0.0214; p=0.049) and nuclear circularity (0.878 vs. 0.885, p=0.026). Circularity (p=0.011) and texture homogeneity (p=0.048) correlated with TMB. ASM texture correlated with PD-L1 expression (p=0.018). The decision tree model for predictive and screening purposes resulted in 0.83 and 0.62 accuracies, respectively. AUC of AI-model for ICI responsiveness resulted in fair (0.74 on average, range 0.55-0.81).

      Conclusion

      Our results indicate the substantial value of the morphological feature as a biomarker for ICI therapy. Morphological characteristics are eligible from archived FFPE samples, showed good correlation to the underlying genetic alteration. Digital pathology can serve useful predictive morphological biomarkers for precision medicine of lung cancer patients, and promising the power of AI-assisted pathology.

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    OA15 - Targeted Agents and Immunotherapy for Small Cell Lung Cancer (ID 152)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
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      OA15.06 - Discussant - OA15.04, OA15.05 (Now Available) (ID 3805)

      14:30 - 16:00  |  Presenting Author(s): Hidehito Horinouchi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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