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Bo Zhu



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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-16 - Predictive Markers for Efficacy in Malignancies Treated with Immune Checkpoint Inhibitors (Now Available) (ID 2171)

      08:00 - 18:00  |  Author(s): Bo Zhu

      • Abstract
      • Slides

      Background

      Predictive markers for tumor response and efficacy of immune checkpoint inhibitors (ICIs) are still controversial. Measurements of the widespread biomarkers, such as PD-L1 expression or tumor mutational burden, are invasive and costly. Therefore, we investigated several accessible factors to predict prognosis.

      Method

      Clinicopathologic features and previous treatment records were collected from 64 patients with diverse malignancies between 2016 and 2018 in oncology department of Xinqiao hospital. Endpoints were progression free survival (PFS) and best overall response (bOR). The best cut-off points of continuous variables were determined by R. Kaplan-Meier was applied to analyze survival. The correlations between bOR and biomarkers were analyzed by Chi-square test.

      Result

      After a median follow-up of 5.5 months, a significant improvement in PFS was observed in 38 patients with higher body mass index (BMI, cut-off=21.45kg/m2) compared to the other 26 patients (10.0 months vs 4.6 months, p=0.015), also the former experienced a tendency of higher bOR rate (28.9% vs 11.5%, p=0.178). Moreover, patients who had radiotherapy records experienced better PFS (12.3 months vs 4.5 months, p=0.019) and higher bOR rate (26.1% vs 19.5%, p=0.542) than the others. Further, receiving antibiotics during immunotherapy was a negative factor in the prognosis of ICIs, which led to worse PFS (4.2 months vs 9.7 months, p=0.019) and lower bOR rate (8.3% vs 25.0%, p=0.383) than its counterparts.wclc.jpg

      Conclusion

      Higher BMI and radiotherapy records are associated with better clinical outcomes of immunotherapy, while receiving antibiotics is negatively correlated with efficacy of ICIs.

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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-10 - Molecular Characterization of NSCLC-Like and SCLC-Like Subsets in Chinese Pulmonary Large-Cell Neuroendocrine Carcinoma (LCNEC) (Now Available) (ID 1341)

      08:00 - 18:00  |  Author(s): Bo Zhu

      • Abstract
      • Slides

      Background

      LCNEC is an aggressive, biologically heterogenous carcinoma which can be molecularly characterized as SCLC-like and NSCLC-like. Accurate distinction of molecular subset is of major clinical relevance since it may guide treatment choices in LCNEC. Here we determined the genomic characteristics of the two LCNEC subsets in a Chinese cohort to clarify their correlations with traditional lung cancer histologies.

      Method

      FFPE samples from 31 LCNECs were sequenced using a 520-cancer-related gene panel, with an average sequencing depth of 1385X. Comparative mutational analysis was conducted between NSCLC-like LCNECs from our cohort and adenocarcinomas from TCGA dataset

      Result

      Despite similar clinical features in terms of stage and age at diagnosis, NSCLC-like (42%, 13/31) and SCLC-like (32%, 10/31) subsets from LCNEC displayed distinct molecular characteristics. NSCLC-like subset harbored significant higher mutation frequencies of STK11, KEAP1 and FAT3 (53.8%, 38.5% and 38.5%, p=.007, .046 and .046), while SCLC-like subset was characterized by highly mutated RB1 (100%, p<.001) and PTEN (50%, p=.007). Compared with TCGA adenocarcinomas, NSCLC-like LCNEC displayed more frequent mutations in TP53, STK11, APC, KMT2D and SMARCA4 (76.9%, 53.8%, 30.8%, 30.8% and 23.1%; p=.043, .004, .045, .005 and .049). In addition, potential targetable alterations were present in 46.2% (6/13) pts of NSCLC-like subset. For those advanced stage pts, 2/5 NSCLC-like and 5/5 SCLC-like pts received relevant chemotherapy according to their molecular characteristics. The clinical outcomes of these pts are still under follow-up.

      Conclusion

      This study demonstrates the distinct molecular features between NSCLC-like and SCLC-like subsets, and highlights the predominant genomic similarity and separate entities between NSCLC-like LCNEC with adenocarcinoma. Given the evidence that genomic profiling may aid in informing treatment decisions for pts with LCNEC, our study indicates that, based on accurate molecular typing, 46.2% NSCLC-like pts may benefit from potential targeted therapy and the rest of them may be more suitable to receive NSCLC-chemotherapy

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    OA03 - Systemic Therapies for SCLC: Novel Targets and Patients' Selection (ID 121)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
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      OA03.05 - Characterization of Genomic Alterations in Chinese LCNEC and SCLC via Comprehensive Genomic Profiling (Now Available) (ID 1486)

      13:30 - 15:00  |  Author(s): Bo Zhu

      • Abstract
      • Presentation
      • Slides

      Background

      LCNEC and SCLC are aggressive neuroendocrine carcinomas with overlap in clinical, histopathologic, morphologic and genomic features. Differential molecular features between the two subtypes have not been well elucidated, contributing the uncertainty for optimal clinical strategy for each subtype. Here we interrogated the genomic characteristics in LCNEC as compared to SCLC along with their histologically related subtypes: carcinoids and atypical carcinoids via comprehensive genomic profiling.

      Method

      FFPE samples from 31 LCNECs, 35 SCLCs, 14 carcinoids and 22 atypical carcinoids were sequenced in a CLIA-certified sequencing laboratory using 520-cancer-related gene panel, with an average sequencing depth of 1385X.

      Result

      Comparative mutational analysis revealed that both LCNEC and SCLC sub-cohorts displayed higher rate of TP53 alterations than that of carcinoid (p<0.001, p<0.001). SCLC patients harbored more RB1 and PIK3CA mutations than LCNECs (p<0.001, p=0.014) and carcinoids (p<0.001, p=0.018). In addition, mutation frequencies of LRP1B, FAT1, PRKDC, PIK3CA, NOTCH1, SPTA1 and EPHA3 in SCLC were significantly higher than that in carcinoid. Mutations in TP53 and RB1 occurred concurrently in 83% (29/35) SCLC patients, whereas in only 32.3% (10/31) LCNECs.(Fig.1) We further investigated the distribution of mutations across KEGG pathways and found that mutation frequencies in both HIF-1 and Notch signaling pathways were lower in LCNEC than SCLC (p=0.032, p=0.025). Copy number variation (CNV) analysis revealed that LCNEC and SCLC had comparable CNVs which were significantly higher than carcinoid (p<0.001, p<0.001) and atypical carcinoid (p=0.010, p=0.028). TMB analysis also revealed a comparable TMB status of LCNEC (12.7/Mb) and SCLC (11.9/Mb), and relatively lower TMB in both carcinoid (2.4/Mb, p<0.001, p<0.001) and atypical carcinoid (5.6/Mb, p=0.003, p=0.009) than LCNEC and SCLC.

      wclc lcnec figure 1.jpg

      Conclusion

      We demonstrated the differential genomic characteristics in the four subtypes of neuroendocrine carcinomas. Compared with SCLC, LCNEC has lower mutation frequencies in RB1, PIK3CA, as well as HIF-1 and Notch signaling pathways. In addition, LCNEC and SCLC had comparable CNV and TMB status, which significantly higher than that of carcinoids and atypical carcinoid.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-126 - The Co-Occurring Genomic Landscape of ERBB2 Exon 20 Insertion in Non-Small Cell Lung Cancer (NSCLC) and the Potential Indicator of Response to Afatinib (Now Available) (ID 1284)

      09:45 - 18:00  |  Author(s): Bo Zhu

      • Abstract
      • Slides

      Background

      Human epidermal growth factor receptor 2 (ERBB2, HER-2) 20 exon insertion (ERBB2ex20ins) has been identified as an oncogenic driver in lung cancer, for which no valid therapy is currently approved. Concurrent alterations may elucidate its refractory features. Previous studies on Afatinib, a pan-ERBB inhibitor, have revealed an inconsistent clinical activity of it for this group of patients.

      Method

      Plasma or tissue samples of 112 patients with ERBB2ex20ins were performed next generation sequencing (NGS) for 59 or 1021 cancer-related genes in a Clinical Laboratory Improvement Amendments-certified Laboratory from July 2016 to December 2018. The sequencing data of MSKCC Cohort was downloaded from the public Cancer Genome Atlas Database. The clinical outcomes of 18 patients receiving Afatinib treatment were collected by each contributing doctor in charge and pooled for analysis.

      Result

      Among the 112 patients, most of cases were female (54%, 60/112) and adenocarcinoma (68%, 76/112). Considering the insertions sites, three subtypes were A775ins (71%; 79/112), G776indel (17%; 19/112) and P780ins (12%; 14/112) in the order of frequency. 80.4% (90/112) of patients had at least one additional alteration. The most frequent co-occurring genes were TP53 (66.1%, 74/112), LRP1B (18.2%, 10/55), EPHA5 (9.1%, 5/55), MLL3 (9.1%, 5/55) and RB1 (8.0%; 9/112). Putative other driver aberrations were mutually exclusive from ERBB2ex20ins. Furthermore, cell cycle pathway was the most commonly involved pathway (84.0%; 94/112) of all the concurrent genes. No substantial differences of concurrence in genomic or pathway level were observed among the three ERBB2 insertion subtypes. The co-occurring genomic feature of ERBB2ex20ins in Our Cohort of Chinese people had an overall strong concordance with the MSKCC Cohort from the United States (R2=0.74, P<0.01). For the prognosis, patients had a worse OS when co-occurring mutation in TP53 [median OS:14.5m (95%CI: 12.7m-16.3m) vs 30.3m (95% CI: not reached)], while the OS was not significantly different among three subtypes. The median duration time for patients with disease control of Afatinib was 4.5 months (95%CI: 3.6m-5.4m; range: 2.5m-13.4m). Of note, ERBB2ex20ins in subclonal status was a significantly independent factor relating to shorter PFS of Afatinib [median PFS: 1.2m (95%CI: 0.8-1.6m) vs 4.3m (95%CI: 3.3m-5.3m), P<0.05]. Dynamic detection in two patients found ERBB2 amplification may be a resistance mechanism for Afatinib.

      Conclusion

      Concurrence of genetic alterations in NSCLC patients with ERBB2ex20ins was common. The complex genomic characteristic should be fully considered by stratifying patients according to potentially relevant co-mutations other than ERBB2 insertion sites in the designing regimens for them. In addition, the therapeutic effect of Afatinib on patient with ERBB2ex20ins is limited, the clonal status of ERBB2ex20ins may be an important factor with prognosis value.

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