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Hironori Yoshida



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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-021 - Efficacy of Single-Agent Chemotherapy after Exposure to Nivolumab in Advanced Non-Small Cell Lung Cancer (ID 8524)

      09:00 - 16:00  |  Author(s): Hironori Yoshida

      • Abstract

      Background:
      Recently, some retrospective studies suggested improvement of clinical outcome of patients with non-small cell lung cancer (NSCLC) receiving chemotherapy after immune checkpoint inhibitor.

      Method:
      We performed a single-center, retrospective study to compare overall response rate (ORR) and progression-free survival (PFS) in NSCLC patients who received single-agent cytotoxic chemotherapy after nivolumab (Group A) with those in NSCLC patients who received single-agent cytotoxic chemotherapy as 3[rd]-line or 4[th]-ine treatment without preceding nivolumab treatment (Group B). Patients with EGFR mutation or ALK rearrangement were excluded from this study.

      Result:
      Fourteen and 61 patients were were included in Group A and Group B, respectively. There were no significant difference of clinical characteristics between the two groups in terms of age, sex, smoking history, performance status and histology. Nab-paclitaxel was most frequently used in group A, while docetaxel was most commonly used in group B. Docetaxel or gemcitabine was significantly highly used in group B (7.1% vs. 54.1%, p < 0.01). The median administered line of nivolumab in Group A was 4. ORR was higher in Group A, but not significantly (14.3% vs. 8.1%, p = 0.610). Median PFS was compatible between the two groups (median, 56 days vs. 63 days, p = 0.425).

      Conclusion:
      Nivolumab might improve the efficacy of subsequent chemotherapy.

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    P2.03 - Chemotherapy/Targeted Therapy (ID 704)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P2.03-055 - Comparison of Afatinib Versus Erlotinib for Advanced Non-Small-Cell Lung Cancer Patients with Resistance to EGFR-TKI (ID 10463)

      09:30 - 16:00  |  Author(s): Hironori Yoshida

      • Abstract

      Background:
      Afatinib, an irreversible ErbB-family blocker, has shown activity for patients with advanced non-small-cell lung cancer (NSCLC) after failure of gefitinib or/and erlotinib in LUX-LUNG1 trial; however, efficacy data of EGFR-TKI re-challenge with afatinib is insufficient.

      Method:
      We retrospectively reviewed medical record of the patients with advanced NSCLC harboring EGFR mutation whose disease progressed after the treatment with gefitinib or erlotinib and received EGFR-TKI re-challenge at Kyoto University Hospital between Apr 2008 and Mar 2017, and compared the efficacy of afatinib after the failure of gefitinib or erlotinib and erlotinib after the failure of gefitinib.

      Result:
      Sixty-two patients were identified, including 13 patients with afatinib and 49 patients with erlotinib. Patient characteristics, such as age, sex, ECOG-PS and smoking status, were not significantly different between the treatment groups. In the afatinib group, 8 patients had received erlotinib as their initial EGFR-TKI and 5 patients had received gefitinib. In the erlotinib group, all patients had received gefitinib as their initial EGFR-TKI. EGFR T790M mutation status was unknown in all patients when EGFR-TKI was re-administrated. Overall response rate (ORR) was 12.7% and disease control rate (DCR) was 54.5% in the entire population. ORR in the afatinib group and the erlotinib group were 7.7% and 14.3%, respectively (p=0.513), and DCR in the afatinib group and the erlotinib group were 61.5% and 52.4%, respectively (p=0.561). Median progression-free survival was 2.4 months in the entire population (95% confidence interval [CI], 1.8-3.3), and 3.9 months in the afatinib group and 2.3 months in the erlotinib group, respectively (hazard ratio [HR] = 0.698 (95% CI, 0.351-1.285), p=0.258).

      Conclusion:
      Re-challenge with EGFR-TKI demonstrated clinical benefit as previously reported. No significant difference was observed between the efficacy of afatinib after the failure of gefitinib or erlotinib and that of erlotinib after the failure of gefitinib.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 3
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      P2.07-003 - Nivolumab for Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer (ID 7914)

      09:30 - 16:00  |  Presenting Author(s): Hironori Yoshida

      • Abstract

      Background:
      Programmed death-1 (PD-1) inhibitor, nivolumab, is one of the standard second-line treatments for advanced non-small cell lung cancer (NSCLC); however, its efficacy for patients with epidermal growth factor receptor (EGFR) mutation is still debatable.

      Method:
      We retrospectively reviewed the medical records of 82 patients with advanced NSCLC who were treated with nivolumab at Kyoto University Hospital between December 2015 and December 2016, and identified 24 patients harboring EGFR mutation. In this analysis, 1) treatment effect was compared between patients with and without EGFR mutation, and 2) clinical characteristics affecting the efficacy of nivolumab were examined in patients with EGFR mutation.

      Result:
      Overall response rate (ORR) was 13% and disease control rate (DCR) was 44% in the entire population. ORR (8% versus 15%, p=0.37) and DCR (25% versus 51%, p=0.024) were lower in patients with EGFR mutation compared with those in patients without EGFR mutation. Median progression-free survival (PFS) was 2.0 months for the entire population (95% confidence interval [CI], 1.73-2.57), and 1.8 and 2.2 months for EGFR mutation-positive and EGFR mutation-negative patients, respectively (hazard ratio [HR]=0.68 (95% CI, 0.4-1.19), p=0.17). In the EGFR mutation-positive population, higher Brinkman index and shorter response duration with precedent EGFR-TKI were correlated with longer PFS with nivolumab. Three patients with EGFR mutation achieved durable disease control lasting more than 1 year, two of whom harbored uncommon EGFR mutation (G719X).

      Conclusion:
      Nivolumab had limited efficacy in EGFR mutation-positive NSCLC patients; however, some patients derived meaningful clinical benefit from nivolumab. Further studies are warranted to elucidate the clinical characteristics predicting the efficacy of nivolumab in this population.

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      P2.07-013 - Efficacy and Safety of Nivolumab in Non-Small Cell Lung Cancer with Preexisting Interstitial Lung Disease (ID 8210)

      09:30 - 16:00  |  Author(s): Hironori Yoshida

      • Abstract
      • Slides

      Background:
      Patients with interstitial lung disease (ILD) have a higher incidence of non-small cell lung cancer (NSCLC) and have few treatment options for NSCLC. While immune checkpoint inhibitors (ICI) are used for NSCLC treatment, the incidence of ICI-related ILD in patients with preexisting ILD is still unknown. Therefore, we retrospectively evaluated the efficacy and safety of nivolumab in patients with NSCLC with preexisting ILD.

      Method:
      We reviewed patients who were administered nivolumab at National Hospital Organization Kyoto Medical Center, Kyoto University Hospital, and Japan Red Cross Fukui Hospital. All patients were initiated on nivolumab therapy between December 24, 2015 and December 31, 2016 and were reviewed until May 31, 2017 or the date of death. We compared the response rate (RR), disease control rate (DCR), overall survival time (OS), incidence of nivolumab-related ILD, and severity of nivolumab-related ILD between patients with and without preexisting ILD.

      Result:
      Of 173 NSCLC patients administered nivolumab, 14 (8%) had preexisting ILD. The major radiographic pattern of preexisting ILD was a non-specific interstitial pneumonia pattern (10 patients), followed by the usual interstitial pneumonia pattern (4 patients). The RR and DCR were 21% and 57% versus 12% and 40% in patients with and without preexisting ILD (p = .393 and p = .263), respectively. The median OS from the initiation of nivolumab was not reached (95% confidence interval [CI], 4.1 months to not analyzed [NA]) with preexisting ILD and was 11.7 months (95% CI, 7.5 months to NA) without ILD (hazard ratio, 0.71; 95% CI, 0.29 to 1.77). The incidence of nivolumab-related ILD was significantly higher with preexisting ILD than without ILD (50% vs 15%, p = .004); however, the incidence of grade 3 or 4 nivolumab-related ILD was not significantly different in those with and without preexisting ILD (14% versus 6.3%, p = .251). The median time to the onset of nivolumab-related ILD was 2.3 months (range, 0.5 to 4.0 months) with preexisting ILD versus 2.4 months (range, 0.03 to 12.4 months) without ILD. No ILD-related death occurred.

      Conclusion:
      Treatment with nivolumab in NSCLC patients with preexisting ILD might offer comparable efficacy to that in those without ILD. Although a higher incidence of nivolumab-related ILD was observed in patients with preexisting ILD, incidence of severe nivolumab-related ILD was not significantly different between those with and without preexisting ILD. Additional studies should be conducted to determine the efficacy and safety of nivolumab in patients with NSCLC with preexisting ILD.

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      P2.07-017 - Association between Thyroid Dysfunction and Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Received Nivolumab (ID 8330)

      09:30 - 16:00  |  Author(s): Hironori Yoshida

      • Abstract

      Background:
      Nivolumab is one of immune-checkpoint inhibitors and has the first agent approved by the U.S. Food and Drug Administration for advanced non-small cell lung cancer (NSCLC). However, the rate of objective responses remains at approximately 20%.Additionally, immune-checkpoint inhibitors often have developed immune-related adverse events. We have previously reported that PD-L1 single nucleotide polymorphisms (SNPs) were possible biomarker for efficacy of nivolumab. We investigated the association between genetic polymorphisms in the PD-1/PD-L1 gene and clinical outcome for nivolumab including response and adverse events.

      Method:
      A total of 68 consecutive patients with NSCLC were treated with nivolumab from December 2015 to October 2016 at Kyoto University. Of these patients, 59 participated in the present study. The remaining 9 patients were excluded from this study because 3 patients declined informed consent, 2 patients had no follow up blood examination, one patient had a history of double cancer and 4 patients had determined as progression disease within 15days from the first administration of nivolumab. Seven SNPs (PD-L1; rs822339, rs1411262, rs2890658, rs4143815, rs2282055, PD-1; rs2227981, rs2227982) were genotyped using TaqMan genotyping assay. Response was assessed as per the Response Evaluation Criteria in Solid Tumors (version 1.1) by investigators respectively. Adverse events were assessed as per the Common Terminology Criteria for Adverse Events (version 4.0) by an investigator. We defined hyperthyroidism as elevated FT4 or FT3 and hypothyroidism as low FT4.We explored the association of adverse events and the PD-1/PD-L1 SNPs subtypes using the Cochrane-Armitage test and Fisher’s exact test as appropriate. Difference of progression free survival (PFS) between each group was assessed using the log-rank test.

      Result:
      Median PFS in this group was 67days (95% confidence interval, 54 to 107 days). Median PFS was significantly longer in patients with thyroid dysfunction than in those without thyroid dysfunction (152 vs 58 days; P = 0.0349). GG and GT genotype of rs2282055 were related to better PFS (82 vs 65 days; P = 0.0311). There were no significant association between thyroid dysfunction and SNPs. However, absence of thyroid dysfunction in patients with TT genotype of rs22282055 suggests that rs2282055 might be related thyroid dysfunction (P=0.1863 Fisher’s exact test).

      Conclusion:
      In the patients treated with nivolumab, GG and GT genotype of rs2282055 might be a predictive biomarker for response and might contribute the occurrence of thyroid dysfunction.