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A. Gupta



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      197TiP - A phase 1/2 trial of selinexor combined with docetaxel for previously treated, advanced KRAS mutant non-small cell lung cancer (ID 244)

      12:30 - 13:00  |  Presenting Author(s): A. Gupta

      • Abstract

      Background:
      Selinexor is an oral, reversible inhibitor of exportin-1 (XPO1), the major nuclear export protein responsible for nucleocytoplasmic transport of multiple tumor suppressor proteins and cell cycle regulators. Upregulation of XPO1 results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical and clinical trials. The most extensively studied SINE to date, selinexor (KPT-330; Karyopharm Therapeutics, Inc., Newton, MA), has demonstrated single-agent anticancer activity and synergistic effects in combination regimens against multiple cancer types. SINE may have particular relevance in KRAS-driven tumors, for which this treatment strategy demonstrates significant synthetic lethality. Thus, we designed a phase 1/2 study to assess the safety and tolerability of selinexor in combination with docetaxel in patients with previously treated, advanced KRAS mutant non-small cell lung cancer (NSCLC).

      Trial design:
      This is a multicenter, single-arm, open-label, non-blinded trial. Eligible patients are aged ≥18 years with advanced NSCLC and by central testing documenting presence of KRAS mutation (codons 12, 13, or 61). We will enroll 9–18 patients in the dose escalation cohort and 35 patients in the expansion cohort at five institutions with UT Southwestern as the primary coordinating center for this study. Dose escalation will be performed in a traditional 3 + 3 design. Patients will receive selinexor orally once weekly, with a lead in period of 1 week before chemotherapy initiation, in combination with standard doses of docetaxel given once every 3 weeks. Treatment will be administered in 21-day cycles. Dose limiting toxicities will be assessed based on the first cycle (7-day lead-in + 21-day cycle = 28 day) toxicity. The primary objective is to determine the safety and the maximum tolerated dose and recommended Phase 2 dose of selinexor administered with the standard dose of docetaxel. The sample size estimate is based on the exact one-sample binomial test for proportions. Enrollment will open in January 2018.

      Clinical trial identification:
      NCT03095612

      Legal entity responsible for the study:
      University of Texas Southwestern Medical Center, Dallas, TX, USA

      Funding:
      Karyopharm Therapeutics, Inc., Newton, MA

      Disclosure:
      L. Horn: Has consulting for Abbvie, Astra Zeneca, Lilly, BMS, Merck, Roche-Genentech, Xcovery. D.E. Gerber: Research funding from Karyopharm. All other authors have declared no conflicts of interest.

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      98P - Trends in and impact of hospital-acquired adverse events in patients with lung cancer undergoing lung resection (ID 341)

      12:30 - 13:00  |  Presenting Author(s): A. Gupta

      • Abstract

      Background:
      Hospital-acquired adverse events are a measure of quality of care delivered and may adversely impact patient outcomes. It is unknown if there been a change in the rates and impact of these adverse events with their increasing recognition as quality measures. We analyzed hospital-acquired adverse events in patients with lung cancer undergoing lung resection using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010.

      Methods:
      NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses, procedures, and dismissal information were abstracted using ICD-9 diagnosis (162.X) and procedure codes (32.9, 32.3X, 32.4X, and 32.5X). The Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) were utilized to identify hospital-acquired adverse events. Weighted analyses were performed using SAS version 9.4.

      Results:
      An estimated 585,408 patients with lung cancer underwent lung resection during the study period and were included in the analysis; 58.3% were >65 years, 49.1% women, 66% white. Of these, 153,609 (26.2%) suffered from ≥1-PSI event during their hospitalization. The proportion of patients suffering from ≥1-PSI event consistently increased from 22.0% in 2001–2002, to 34.8% in 2009–2010, p value <0.01. Compared to those with no PSI, patients with ≥1-PSI experienced higher in-hospital mortality (2.2%, vs 15.7%, adjusted odds ratio, 7.8, 95% CI 5.1–11.8), and prolonged length-of-stay (7.8 days, vs 12.5 days, adjusted mean difference, 4.6 days, 95% CI 3.7–5.5), p value for both <0.01.

      Conclusions:
      There was a substantial increase in the frequency of potentially avoidable adverse events in this national database of lung cancer patients undergoing resection, associated with worse outcomes. Although this may in part be due to increasing recognition, interventions are required to prevent these potentially avoidable events.

      Clinical trial identification:
      Not applicable

      Legal entity responsible for the study:
      Arjun Gupta

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.