Author of

• 30446

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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
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 30452

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    P1.01-04 - A Phase II Trial of Weekly Nab-Paclitaxel in the Salvage Setting for Advanced Non-Small Cell Lung Cancer: Results of NICE Salvage Study   (ID 1534)

    09:45 - 18:00  |  Author(s): Toshiaki Takahashi
    • Abstract

    Background
    

    The optimal treatment in patients with advanced non-small cell lung cancer (NSCLC) after failing second- or third-line chemotherapy, i.e. NSCLC in salvage setting, has yet to be established. A small study reported that solvent-based paclitaxel (sb-P) monotherapy was safe and efficacious and could be a treatment option for NSCLC in salvage setting (Anticancer Res 2005).  Nanoparticle albumin-bound paclitaxel (nab-P) showed a higher overall response rate (ORR) and better tolerability than sb-P when combined with carboplatin (CBDCA) as a first-line chemotherapy (J Clin Oncol 2012). These results suggest that nab-P monotherapy could be better therapeutic option than sb-P monotherapy for NSCLC in salvage setting. We therefore planned NICE Salvage study aiming to assess the efficacy and safety of nab-P monotherapy for NSCLC patients in salvage setting. 

    Method
    

    NICE Salvage study was a multicenter single arm phase II study. Eligibility criteria included patients aged >= 20 years, with PS 0-2 and adequate organ function, and who have failed two or three prior lines of chemotherapy including at least a platinum-containing regimen for pathologically-proven advanced NSCLC. Patients who had treatment history with sb-P or nab-P, or had tumors harboring EGFR mutation or ALK fusion gene were excluded. Nab-P was administered at a dose of 80 mg/m² on days 1,8 and 15 of a 28-days cycle and repeated until progressive disease, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), ORR, disease control rate (DCR), efficacy according to prior use of docetaxel, quality of life, and safety. The study is powered to detect a 1.5-month improvement in median PFS in the investigational arm beyond the 2.0-month median PFS estimated from historical data. Assuming a one-sided 0.10 level of Type I error and 80% power, target sample size is calculated at 35.  (UMIN000016173).

    Result
    

    Thirty-eight patients were enrolled and a patient was excluded from efficacy and safety analysis. Patient’s characteristics (n = 38) were as follows: median age = 68 years, male/female = 31/7, adenocarcinoma/squamous cell carcinoma /others = 20/15/3. Median PFS and OS was 3.5 month (95% confidence interval (CI), 1.7-3.8), and 13.4 month (95%CI, 9.1-25.1), respectively. ORR and DCR were 10.8% (95%CI, 2.9-24.8 ) and 56.8% (95%CI, 38.3-71.3 ), respectively. Grade 3 or 4 treatment-related adverse events were neutropenia (10.8%), anemia (2.7%), hepatotoxicity (2.7%) and diarrhea (2.7%). One treatment-related death (pulmonary infection) was observed.

    Conclusion
    

    This study failed to meet predefined primary endpoint. However the results showed that nab-P monotherapy was moderately efficacious and well-tolerated, suggesting the need for further investigation for NSCLC in salvage setting.

• 30943

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  P2.04 - Immuno-oncology (ID 167)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30989

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    P2.04-41 - Clinical and Immunological Factors Associated with Mutation Burden in Non-Small Cell Lung Cancer (ID 1313)

    10:15 - 18:15  |  Author(s): Toshiaki Takahashi
    • Abstract

    Background
    

    It is unclear whether factors including clinical and immune microenvironment (IME) are associated with tumor mutation burden (TMB) in patients with non-small cell lung cancer (NSCLC). We aimed to develop a prediction model to identify the association between these factors and TMB in patients with NSCLC.

    Method
    

    We assessed somatic mutation burden in surgical tumor specimens with whole exome sequencing (WES) using an ion torrent proton platform (Thermo Fisher Scientific). The IME profiles including PD-L1 tumor proportion score (TPS), stromal CD8 tumor infiltrating T cell (TIL) density, and stromal Foxp3 TIL were quantified by digital pathology using a machine learning algorithm. To detect factors associated with TMB, factors including clinical and IME were assessed using a multipul regression model. Two hundred NSCLC patients, for whom both WES and clinical data from Project HOPE (High-Tech-Omics-based Patient Evaluation) were available, excluding those with low tumor purity (less than 20%), were assessed in this study.

    Result
    

    Out of 250 NSCLC patients with tumors surgically resected between September 2014 and September 2015, we analyzed tumors from 200 patients. Patient background: median age (range) 70 (39-87), male 37.5%, smoker 27.5%, pathological stage (p-stage) (I/ II/ III) 63.5/22.5/14.0% respectively, histological type (Ad/Sq) 77.0/23.0%, primary tumor location (upper/lower) 58.5/41.5%, median standardized uptake value (SUV) 7.5 (0.86-29.8), median serum CEA level (range) 3.4 ng/ml (0.5-144.3), median serum CYFRA 21-1 level 1.2 ng/ml (1.0-38.0), median TMB 2.19/ Mb (0.12-64.38), median PD-L1 TPS 15.1% (0.09-77.4), median stromal CD8 TIL 582.1/mm² (120.0-4967.6), and median stromal Foxp3 TIL 183.7/mm² (6.3-544.0).

    In simple regression analysis, gender (male/female), smoking status (yes/no), p-stage (I/II,III,IV), age (< 70, ≥70), primary tumor location (lower/upper), serum CEA level (low [< 5.0ng/ml], high [≥ 5.0 ng/ml]), serum CYFRA level (low [< 3.5ng/ml], high [≥3.5 ng/ml]), and actionable mutation status (Mt+/Mt-) were favorable prognostic factors (p < .0001, p = .0001, p = .072, p = .027, p = .045, p = .002, p = .009, and p = .069 respectively).

    Multiple regression analysis identified five factors [smoking status: smoker, age: less than 70, primary tumor location: lower, serum CEA level (greater than 5ng/ml), and serum CYFRA level (greater than 3.5ng/ml)] associated with higher TMB (p = .002, p = .045, p = .03, p = .046 and p = .016 respectively).

    Conclusion
    

    IME factors did not associate with tumor mutation burden. However, along with smoking, lower primary location, elevated CEA and CYFRA level may be independent predictors of high TMB.