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Katsuyuki Hotta



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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • 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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      P2.06-10 - Combination Chemotherapy with Cisplatin, Pemetrexed, and Nivolumab for Malignant Pleural Mesothelioma: A Trial in Progress (ID 12210)

      16:45 - 18:00  |  Author(s): Katsuyuki Hotta

      • Abstract
      • Slides

      Background

      Combination chemotherapy with cisplatin and pemetrexed is the standard treatment regimen for malignant pleural mesothelioma (MPM); however, the median overall survival (OS) is just about 12 months. Additional treatment options are urgently needed. The aim of this study is to assess the efficacy and safety of combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable MPM.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a single-arm, prospective, non-randomized, non-comparative, open label, multicenter, phase II trial. This study will assess the efficacy and safety of the first-line combination therapy of cisplatin, pemetrexed, and nivolumab for advanced or metastatic MPM. Key inclusion criteria includes 1) age older than 20 years, 2) pathologically-confirmed MPM, 3) measurable lesion designated by modified RECIST criteria, 4) tumor sample available to test for Programmed Death-Ligand 1 (PD-L1) expression, 5) Eastern Cooperative Oncology Group Performance Status is 0 or 1. Combination chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/body) is administered every 3 weeks for a total of 4 to 6 cycles. Then, maintenance therapy with nivolumab will be administered until disease progression, unacceptable toxicities, or the patient’s condition meets the withdrawal criteria. The primary endpoint is the centrally-reviewed overall response rate. The secondary endpoints include the disease control rate, overall survival, progression-free survival. Safety and adverse events will also be evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      This phase II trial commenced in January 2018. A total of 18 patients will be enrolled from four Japanese institutions within 1 year.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first prospective trial to evaluate the effect of an anti-PD-1 antibody combined with cisplatin and pemetrexed for unresectable MPM. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000030892.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • 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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      P2.13-18 - A Multicenter Prospective Biomarker Study to Explore Mechanisms of Afatinib Resistance Based on Digita PCR and Next-Generation Sequencing (ID 12187)

      16:45 - 18:00  |  Author(s): Katsuyuki Hotta

      • Abstract

      Background

      Afatinib is an oral irreversible blocker of ErbB-family kinases and shows a pronounced anti-tumor efficacy for advanced non–small cell lung cancer (NSCLC) positive for activating mutations of EGFR. We applied digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS) to explore mechanisms of afatinib resistance.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible patients had advanced lung adenocarcinoma with EGFR activating mutations. Tumor and plasma samples were collected before afatinib treatment and after treatment failure with disease progression (systemic progressive disease, SPD). DNA from the samples was analyzed by dPCR and NGS.

      4c3880bb027f159e801041b1021e88e8 Result

      Thirty-five patients were enrolled, with a median follow-up time of 15.8 months. Among 25 patients with SPD, tumor, plasma, or both samples were available for 18, 23, and 16 individuals, respectively. dPCR and NGS detected EGFR T790M mutation in 13 (56.5%) and 11 (47.8%) of 23 plasma samples at SPD, with sensitivity and specificity compared with tumor samples being 83.3% and 70.0% (dPCR) and 50.0% and 70.0% (NGS), respectively. Applying the ratio of the number of T790M alleles to that of activating mutations (T/A) for determination of the T790M positivity improved the sensitivity and specificity of plasma analysis compared with tumor analysis to 83.3% and 100% (dPCR) and 57.1% and 100% (NGS), respectively. Among 25 patients with SPD, the T790M mutation of EGFR alone (n = 11), copy number gain (CNG) of NRAS (n = 1), CNG of MET (n = 1), CNG of EGFR plus T790M (n = 1), and CNG and E545K of PIK3CA plus T790M of EGFR (n = 1) were identified by NGS as putative resistance mechanisms against afatinib. No tumor showed transformation to small cell carcinoma. Median progression-free survival was longer in patients with than in those without T790M at SPD (15.1 versus 10.9 months, P =0.25). Median time to SPD was much longer in patients with than in those without T790M at SPD (17.9 versus 10.9 months, P =0.18).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Assessment of T/A ratio with dPCR or NGS improved specificity of plasma analysis for determination of T790M positivity compared with tumor analysis. dPCR and NGS analysis in tumor and plasma samples shed light on exploring mechanisms of afatinib resistance.

      6f8b794f3246b0c1e1780bb4d4d5dc53