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Jiuwei Cui



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.22a - Tislelizumab Combined With Chemotherapy as First-Line Treatment in Chinese Patients With Advanced Lung Cancer (ID 14702)

      11:15 - 11:15  |  Author(s): Jiuwei Cui

      • Abstract

      Abstract not provided

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-36 - Tislelizumab Combined With Chemotherapy as First-Line Treatment in Chinese Patients With Advanced Lung Cancer (ID 12092)

      16:45 - 18:00  |  Author(s): Jiuwei Cui

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors have shown efficacy in patients with NSCLC as monotherapy and in combination with chemotherapy. Tislelizumab is a humanized IgG4 monoclonal antibody to PD‑1 specifically engineered to minimize FcϒR binding on macrophages, possibly minimizing negative interactions with other immune cells. In a phase 1 study, tislelizumab was generally well tolerated and showed antitumor activity; 200mg IV Q3W was established as the recommended dose.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This multi-arm phase 2 study, consisting of safety run-in and dose-extension phases, assessed tislelizumab in combination with platinum-based chemotherapy (by tumor histology) as a potential first-line treatment for Chinese patients with lung cancer. All patients received tislelizumab at 200mg Q3W in combination with 4–6 cycles of platinum-doublet until disease progression. Nonsquamous (nsq) NSCLC patients received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, while squamous (sq) NSCLC patients received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and small-cell lung cancer (SCLC) patients received etoposide + platinum Q3W. Tumor response (RECIST v1.1) and safety/tolerability were evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 21 Feb 2018, 48 patients (median age, 62 years [range: 36–75], 71% male, 71% current/former smokers) received tislelizumab treatment (median, 3 cycles [range: 1–7]); 44 patients remain on the study. Across the four cohorts, confirmed and unconfirmed partial responses were observed in 13 and 9 patients, respectively (Table). The most frequent AEs were chemotherapy-related hematologic toxicities. The most commonly reported grade ≥3 treatment-related AEs were neutropenia (20.8%) and anemia (12.5%); the most common grade 3 immune-related AEs were pyrexia (6.3%) and rash (6.3%). One sq‑NSCLC patient experienced a fatal myocarditis/myositis following one cycle of paclitaxel/cisplatin; all other treatment-related AEs were managed/resolved by study-drug interruption (n=15) or discontinuation (n=4) and appropriate treatment.

      Best Overall Response (Patients With ≥1 Post-Baseline Tumor Assessment)

      nsq-NSCLC (n=9)

      sq-NSCLC [A] (n=12 )

      sq-NSCLC [B] (n=5 )

      SCLC (n=8)

      Total

      (N=34)

      PR

      4 (44.4)

      9 (75)

      4 (80)

      5 (62.5)

      22 (64.7)

      Confirmed PR

      1 (11.1)

      4 (33.3)

      4 (80)

      4 (50)

      13 (38.2)

      Unconfirmed PR

      3 (33.3)

      5 (41.7)

      0 (0)

      1 (12.5)

      9 (26.5)

      SD

      3 (33.3)

      2 (16.7)

      1 (20)

      2 (25)

      8 (23.5)

      PD

      1 (11.1)

      0 (0)

      0 (0)

      1 (12.5)

      2 (5.9)

      NE

      1 (11.1)

      1 (8.3)

      0 (0)

      0 (0)

      2 (5.9)

      Data presented as n (%).

      Abbreviations: nsq-NSCLC, non-squamous non-small cell lung cancer; NE, not evaluable; PD, progressive disease; PR, partial response; SCLC, small cell lung cancer; SD, stable disease; sq-NSCLC, squamous non-small cell lung cancer.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Tislelizumab, in combination with platinum doublets, demonstrated preliminary antitumor activity and was generally well tolerated in patients with advanced lung cancer.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • 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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      P2.01-26 - Association of Base Excision Repair Gene Polymorphisms with Response to Chemotherapy of Advanced Non Small-Cell Lung Cancer (ID 13805)

      16:45 - 18:00  |  Author(s): Jiuwei Cui

      • Abstract
      • Slides

      Background

      Base excision repair (BER) plays an important role in the maintenance of genome integrity and anti-cancer drug resistance. This study aims to explore the role of BER genes polymorphisms in response to chemotherapy of advanced non small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      During the period from November 2009 to January 2016, a total of 152 patients diagnosed with IIIB or IV stage NSCLC in the First Hospital of Jilin University were admitted into our study. The XRCC1 G28152A, MUTYH G972C, HOGG1 C1245G, PARP1 T2444C polymorphisms of all the patients were detected by the mass spectrometry. And the relationship between BER genes polymorphisms and the response of platinum-based chemotherapy is analyzed by Logistic regression.

      4c3880bb027f159e801041b1021e88e8 Result

      Logistic regression model shows that the response rate of chemotherapy of the PARP1 T2444C polymorphisms, CC genotype (OR: 5.216, 95%CI: 1.568-17.352, P= 0.007) and TC genotype (OR: 2.692, 95%CI: 1.007-7.198, P=0.048) is significantly higher than that of TT wild type, as well as the genotype of TC together with CC (OR: 3.178, 95%CI:1.229-8.219, P = 0.017). There is no relationship between G28152A, MUTYH G972C, XRCC1 HOGG1 C1245G gene polymorphism and chemosensitivity.

      8eea62084ca7e541d918e823422bd82e Conclusion

      PARP1 2444 mutation allele C might be associated with the decreased sensitivity to platinum based chemotherapy in advanced NSCLC. Our findings may be helpful towards designing individualized cancer treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-04 - Prognostic Value of MHC-I, PD-L1 and CD8+ TILs Expressions in Patients with Surgically Resected Non-Small Cell Lung Cancer (ID 13957)

      12:00 - 13:30  |  Author(s): Jiuwei Cui

      • Abstract
      • Slides

      Background

      Lung cancer is the most commonly diagnosed cancer and also the leading cause of cancer death globally. Chemotherapy showed limited improvement in the survival of surgically resected non-small cell lung cancer (NSCLC) patients. There was no effective prognostic indicators in surgically resected NSCLC. The expression levels of tumor surface molecules, such as major histocompatibility complex class I (MHC-I), programmed cell death-ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) were detected in this study to investigate the potential prognostic markers in the patients with surgically resected NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue of 125 patients with surgically resected NSCLC were obtained from the First Hospital of Jilin Universtiy. MHC-I, PD-L1 and CD8+ TILs expressions were detected with immunohistochemistry. The association between their expression levels and patients’ prognosis was analyzed by SPSS 17.0 software (SPSS, Chicago, IL).

      4c3880bb027f159e801041b1021e88e8 Result

      MHC-I was down-expressed, PD-L1 was up-regulated in NSCLC compared with the adjacent tissues. CD8+ TILs could be seen in tumor stroma and nest. With univariate analysis, we found that the down-expression of MHC-I had an association with poor relapse-free survival (RFS) and overall survival (OS) in NSCLC patients (P = 0.007 and P = 0.001). RFS and OS in PD-L1− group tended to be longer than that of PD-L1+ group, but the difference was not significant (P > 0.05). Based on the distribution of CD8+ TILs, patients were divided into three groups: immune-inflamed group, immune-excluded group and immune-desert group. RFS and OS of patients with the immune-inflamed phenotype (CD8inflamed) were longer than patients with the immune-excluded and immune-desert phenotype (CD8non-inflamed) (P = 0.013 and P = 0.015). Besides, patients were divided into four subgroups based on the PD-L1 and CD8+ TILs expression: PD-L1+/CD8inflamed, PD-L1+/CD8non-inflamed, PD-L1−/CD8inflamed, and PD-L1−/CD8non-inflamed. Statistical differences were achieved both in RFS and OS (P = 0.012 and P = 0.032). RFS and OS in patients with PD-L1+/CD8inflamed and PD-L1−/CD8inflamed were longer than patients with PD-L1+/CD8non-inflamed and PD-L1−/CD8non-inflamed. Patients with PD-L1+/CD8non-inflamed experienced the worst RFS and OS. With multivariate analysis, we found that MHC-I and CD8+ TILs might be independent prognostic factors in surgically resected NSCLC.

      8eea62084ca7e541d918e823422bd82e Conclusion

      MHC-I and CD8+ TILs expression had a close association with patients prognosis in this study. The combination of PD-L1 and CD8+ TILs, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. It worth further study to confirm the clinical value of MHC-I, PD-L1 and CD8 TILs expressions in the patients with surgically resected NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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