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Yuchen Han



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    JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)

    • Event: WCLC 2019
    • Type: Joint IASLC-CSCO-CAALC Session
    • Track:
    • Presentations: 1
    • Now Available
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      JCSE01.11 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 3425)

      07:00 - 11:15  |  Author(s): Yuchen Han

      • Abstract
      • Presentation
      • Slides

      Abstract
      Background
      Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).

      Methods
      Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.

      Results
      From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.

      Conclusion

      In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.

      table 1.jpg

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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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      P1.04-02 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 939)

      09:45 - 18:00  |  Author(s): Yuchen Han

      • Abstract
      • Slides

      Background

      Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).

      Method

      Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.

      Result

      From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.

      Conclusion

      In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.

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    P1.09 - Pathology (ID 173)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.09-05 - ALK Testing in Chinese Advanced NSCLC Patients: A National-Wide Multicenter Prospective Real-World Data Study (The RATICAL Study) (ID 1800)

      09:45 - 18:00  |  Author(s): Yuchen Han

      • Abstract

      Background

      ALK-tyrosine kinase inhibitors increase ORR and PFS times in ALK-fusion positive NSCLC patients. It is therefore crucial to assess the efficacy of different methods for detecting ALK rearrangement. At present, there are most testing methods approved by cFDA to detect ALK rearrangement in China. However, many issues regarding to the procedure and quality control (QC) data of ALK testing in the routine clinical practice is still to be studied. This study is to evaluate the ALK testing platforms, testing procedures, result interpretation quality control and clinicopathological characteristics of ALK positive patients in the real world for Chinese lung cancer patients, and achieve expert consensus on the clinical practice of ALK testing.

      Method

      Top 31 hospitals with lung cancer patients in China will participate in the study. All advanced NSCLC subjects who received ALK gene test and all ALK positive NSCLC patients who received surgical treatment from Oct. 2018 to Dec. 2019 will be enrolled. The testing platforms include IHC-VentanaFISHRT-PCR and NGS. It is expected to enroll a total of 30,000 cases, and the clinicopathological information of the patients will be collected. Ring study and interpretation training will be conducted before the study initiated. When 2,000 and 10,000 cases are enrolled, the interim summary and quality control will be conducted respectively. The results were the interim summary and quality control results of 2,000 cases.

      Result

      The 2263 enrollees (mean age, 63 years) included 1365 males (60.32%) and 907 females (39.68%). 205 (of 2263, 9.06%) cases were ALK positive. The ALK positive rate of females (11.10%) was significantly higher than that of males (7.74%). The ALK positive rate of non-smoking patients (11.54%) was significantly higher than that of smoking patients (5.70%). In addition to ALK, the positive rate of EGFR, KRAS, ROS1, HER2, MET, RET and BRAF gene alterations was 46.05%, 9.52%, 3.13%, 3.09%, 2.98%, 2.12% and 0.94%, respectively. Total rate of all driver gene mutation was 60.37% in males, while it was 91.71% in female. Total rate of all driver gene mutation was 59.77% in smoking patients and 90.44% in non-smoking patients. Concurrent mutation of ALK with EGFR, KRAS or ROS1 was 0.33%, 0.45% and 0.22%, respectively. The fusion of EML4-ALK accounted for 75%. The inconsistency rate of IHC-Ventana with FISH, RT-PCR, NGS was 95.07%, 91.30% and 95.45%, respectively. For ALK IHC quality control, 109 slides were used for ring study, and 31 pathologists participated in the interpretion. Among 60 negative cases, 25 cases (41.7%) were diagnosed as positive (false positive) by at least one pathologist. Among 49 positive cases, 12 cases (24.5%) were diagnosed as negative (false negative) by at least one pathologist; 34 cases (31.2%) were diagnosed as inconclusive by at least one pathologist. There were 3.5% and 1.1% of cases found to be misinterpreted during the internal QC and regional QC, respectively.

      Conclusion

      NSCLC patients harboring ALK gene translocation have unique clinicopathological characteristics. Some problems will still be encountered in the real world clinical practice of ALK testing, which need to be guided by establishment of expert consensus.

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      P1.09-31 - Clinicopathological Features and Genomic Profiling of Pulmonary Blastoma with High-Grade Fetal Adenocarcinoma Component (ID 1615)

      09:45 - 18:00  |  Author(s): Yuchen Han

      • Abstract
      • Slides

      Background

      Pulmonary blastoma (PB) is a very rare subtype of sarcomatoid carcinoma with typically low-grade fetal lung adenocarcinoma (L-FLAC) and primitive mesenchymal components. Very few cases of PB contain the high-grade fetal lung adenocarcinoma (H-FLAC) component. The present study was designed to investigate the clinicopathological characteristics and the genomic heterogeneity of epithelial and mesenchymal in PB with H-FLAC.

      Method

      Three surgically resected PB cases with H-FLAC component were enrolled in the study. The epithelial of the first case consisted of mostly H-FLAC mixed with limited amount of L-FLAC. The other two PB tumors contained pure H-FLAC and mesenchymal components. Clinic-pathologic information and prognostic data were retrospectively reviewed. Diagnostic immunohistochemistry was performed. The epithelial and mesenchymal components were macroscopically dissected to profile the genetic alterations separately using capture-based targted sequencing. A commercialized panel, consisting of 520 cancer-related genes, was used.

      Result

      The cells of H-FLAC components in PB showed obvious atypia with more necrosis and enteric adenocarcinoma-like morphology. The squamoid morules were absent in H-FLAC. Proliferation index of the H-FLAC components (30%-80%) was higher than that of the mesenchymal (15%-20%). No aberrant nuclear expression of β-catenin protein and missense mutation in exon 3 of CTNNB1 gene were observed in H-FLAC and all mesenchymal cells. Within a tumor, epithelial and mesenchymal components exhibited relatively comparable molecular profile. In patient 1, 4 mutations: PB1, FAT3, PTCH1 and LRP1B were shared by both epithelial and mesenchymal components. Epithelial component had additional mutations in BCOR, CTNNB1, CTCF, FAT1 and DICER1. In patient 2, 12 mutations were shared. The epithelial component had BRCA2 mutations and the mesenchymal component had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN and RICTOR. Patient 3 had 6 shared mutations. The epithelial component had an additional mutation in KAT6A and the mesenchymal had an additional mutation in APC. Furthermore, both epithelial and mesenchymal components showed significant interpersonal heterogeneity. In other words, the mutation spectrum of the same component (epithelial or mesenchymal )varies significantly among patients. Surprisingly, not a single common mutation was found in the same component among the 3 patients.

      Conclusion

      Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor. In addition, we also observed significant inter-personal heterogeneity of the same component among different patients. Parallel detection of genetic abnormalities in epithelial and mesenchymal could provide further evidence to clarify the histopathological difference and molecular heterogeneity in pulmonary blastoma.

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