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EISHIN Hoshi



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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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      P1.04-54 - Inter-Tumor Heterogeneity of PD-L1 Expressions in Non-Small Cell Lung Cancer (ID 48)

      09:45 - 18:00  |  Author(s): EISHIN Hoshi

      • Abstract
      • Slides

      Background

      Following to approval of Pembrolizumab for patients with advanced NSCLC, PD-L1 IHC 22C3 pharmDx (Dako) was adopted as a companion diagnostic test. While PD-L1 IHC 28-8 pharmDx (Dako) was established as a complementary diagnostic for Nivolumab. Recently many groups demonstrated the intra-tumor heterogeneity of these PD-L1 expressions, but there have been a few reports about the intra-patient or inter-tumor heterogeneity. We aimed to investigate the inter-tumor heterogeneity of PD-L1 IHC 22C3 and 28-8 pharmDx (Dako).

      Method

      Between December 1, 2014 and May 7, 2018, total 517 patients with NSCLC underwent surgical resection at our hospital. We excluded all patients with no informed consent, with no lymph node metastasis, with chemotherapy/radiotherapy before surgery and with never enough volume of material for genetic testing. Finally 35 formalin-fixed paraffin-embedded primary tumors with paired metastatic lymph nodes were available in this study. After staining by PD-L1 IHC 22C3 and 28-8 pharmDx (Dako) respectively, we counted tumor cells exhibiting membrane staining and calculated Tumor Proportion Score (TPS). Afterward, all cases were classified into three subgroups as follows; No Expression (TPS: <1%), Low Expression (TPS: 1-49%) and High Expression (TPS: ≥50%).

      Result

      Average age of 35 patients was 66.8 years old and there were 10 females (28.6%), 10 never smokers (28.6%), 27 adenocarcinomas (77.1%) and 11 tumors with EGFR mutation. The number of cases in No Expression, Low Expression and High Expression in 22C3 were 7 (20.0%), 22 (62.8%) and 6 (17.1%) in primary tumor, meanwhile 18 (51.4%), 13 (37.1%) and 4 (11.4%) in metastatic lymph node, respectively. The concordant rate was 28.6% between TPS subgroups in primary tumor and that in metastatic lymph node. About 28-8 antibody, No Expression, Low Expression and High Expression were 8 (22.9%), 21 (60.0%) and 6 (17.1%) in primary tumor, meanwhile 18 (51.4%), 11 (31.4%) and 6 (17.1%) in metastatic lymph node, respectively. The concordant rate was 31.4% between TPS subgroups in primary tumor and that in metastatic lymph node.

      Conclusion

      Our result demonstrated apparent discrepancy of TPS between primary tumor and metastatic lymph node in both PD-L1 IHC 22C3 and 28-8.

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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
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-95 - Updated Data of KRSG 1302 Study: Nedaplatin and Nab-Paclitaxel for Patients with Previously Untreated Advanced Squamous Cell Lung Cancer (Now Available) (ID 136)

      10:15 - 18:15  |  Author(s): EISHIN Hoshi

      • Abstract
      • Slides

      Background

      Background: Nedaplatin (N) and nab-paclitaxel (nab-P) are efficacious for the treatment of non-small cell lung cancer, especially advanced squamous cell lung cancer. Although a combination of N and nab-P is expected to result in the treatment of squamous cell lung cancer, no sufficient and reliable data have been reported yet.

      Method

      Patients and methods: The inclusion criteria were no prior chemotherapy; stage IIIB or stage IV squamous cell lung cancer; a performance status (PS) of 0–1; 75 > patients’ age > 20 years; and adequate major organ function. Patients received escalating doses of nab-P under a fixed dose of N (100 mg/m2, 1st day) every 3 weeks in phase I. The initial dose of nab-P was 100 mg/m2 on the 1st and 8th day (level 1), and the next dose was 100 mg/m2 on the 1st, 8th, and 15th day (level 2). In phase II, the patients received the recommended dose of N/nab-P. The primary endpoint was tumor response, which was measured according to the revised version of response evaluation criteria in solid tumors.

      Result

      Results: In this study, 5 patients were enrolled in the phase I. Three patients in level 1 experienced no dose-limiting toxicities (DLTs); whereas, 2 patients in level 2 experienced DLTs. Therefore, level 1 was named the recommended dose. In addition, 23 patients were enrolled in phase II. Three and 23 patients in level 1 and phase II were evaluated, respectively. However, among them, 2 of 26 patients were not assessed due to pneumonia, and 1 of 26 patients was excluded from analysis due to patients’ refusal. Partial response, stable disease, and progressive disease were noted in 21, 0, and 2 patients, respectively, yielding a response rate of 91.3% [95% confidence interval (CI): 72.0–98.9]. The median progression-free survival (PFS) was 223 days (95%CI: 144–330), and the median overall survival (OS) was 358 days (95% CI: 255–950). The 1- and 2-year PFS rate were 17.8% and 12.0%. The 1- and 2-year OS rate were 50.0% and 43.8%, respectively. The grade 3 and grade 4 toxicities were manageable and there was no treatment-related death. These data were published in 2018 ESMO. We will report updated efficacy and safety of N/nab-P in KRSG 1302 study.

      Conclusion

      Conclusions: A combination of N (100 mg/m2, 1st day) with nab-P (100 mg/m2, 1st and 8th day) every 3 weeks demonstrated an effective therapeutic approach. Therefore, N/nab-P administration is to be safe and efficacious for patients with advanced squamous cell lung cancer.

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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-17 - Analysis of Lung Adenocarcinoma EGFR Mutation by LAMP Method: Comparison with PCR Method and Identification of a Novel Exon19 Deletion Mutation (Now Available) (ID 69)

      10:15 - 18:15  |  Author(s): EISHIN Hoshi

      • Abstract
      • Slides

      Background

      Detection of EGFR mutation has been widely used for the lung cancer treatment. The accuracy of detecting EGFR mutations is, therefore, very important. We here adopted a method of Loop-mediated isothermal amplification (LAMP) used for the detection of bacteria, which amplifies DNA with high specificity and efficiency under isothermal conditions. So that we evaluated the usefulness of LAMP for detecting various EGFR mutations using cancer tissues in comparison to conventional PCR technique.

      Method

      We enrolled 59 surgically resected lung adenocarcinoma patients. We used Therascreen EGFR PCR Kit as a conventional PCR. Then, we tried to detect EGFR mutations for those specimens using LAMP method, and compared the result of LAMP to that of Therascreen.

      Result

      26 cases had no mutation in the analysis using Therascreen and LAMP method. In 32 cases which showed positive mutations according to Therascreen, and LAMP method, however, we found a single case showing no mutations by LAMP method, and exon 19 deletion by Threascreen. The direct sequence analysis revealed no mutations in the case as shown with LAMP method. Here, we repeated several experiments using LAMP method for the purpose of comfirmation of EGFR status of the case. These additional tests revealed Exon 19 deletion using the LAMP method, moreover, another direct sequencing discovered a novel EGFR mutation. Sensitivity for LAMP method was calculated as 97.0%, specificity as 100%, positive predictive value (PPV) was 100%, negative predictive value (NPV) was 96.3 % and accuracy was 98.3%.

      Conclusion

      The accuracy of detecting EGFR mutation in LAMP method was nealy equivalent to that in Therascreen. Moreover, we detected a novel EGFR exon 19 deletion mutation with the direct sequence.

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