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Maria Jove



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    MA13 - Going Back to the Roots! (ID 139)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA13.03 - Retrospective Study of Intrathecal Therapy for Non-Small Cell Lung Cancer (NSCLC) Patients with Leptomeningeal Carcinomatosis (Now Available) (ID 2086)

      14:00 - 15:30  |  Author(s): Maria Jove

      • Abstract
      • Presentation
      • Slides

      Background

      Leptomeningeal carcinomatosis (LMC) is a devastating cancer-related neurological complication with poor prognosis. In EGFR-mutant (mut) NSCLC patients (pts), osimertinib achieves high penetration into cerebral-spinal fluid (CSF) and promising efficacy. However, for EGFR-mut T790M-negative pts treated with prior 1st- and 2nd-generation tyrosine kinase inhibitors (TKI) and for driver negative NSCLC pts, a combination of intrathecal therapy (IT) and systemic therapy (ST) seems to be an appropriate approach. Our purpose is to explore the clinical outcome of IT combined with ST among NSCLC with LMC depending on EGFR status.

      Method

      NSCLC pts with LMC treated with IT in our institution between 2010 and 2018 were retrospectively studied. After LMC diagnosis, intrathecal methotrexate (scheduled: 12mg twice weekly for 4 weeks, then 12mg weekly for 4 weeks) was given in combination with ST. A Kaplan-Meier survival analysis was performed for overall survival (OS) and progression free survival (PFS).

      Result

      A total of 39 pts were included. Patient’s clinical characteristics are summarized in table 1. EGFR status was 17 mut (del19: 11pts); 11 wild-type (wt) and 11 unknown (unk). LMC and NSCLC diagnosis were more likely to be synchronous in EGFR wt compared with EGFR mut. The median follow-up from LCM diagnosis was 10.2 months. At the time of this analysis, only 6 pts were alive. Thirty-two pts received ST in combination with IT, 18 (46%) pts chemotherapy (6wt/ 3mut/ 9unk), while 14 (36%) pts an EGFR TKI (1wt/ 13mut). Clinical response (improvement of neurological symptoms and/or KPS) was seen in 11 (65%) EGFR mut pts vs 2 (18%) wt pts (p=0.033). Median OS and PFS for the whole cohort were 23 weeks (95%CI, 8.1 to 37.9) and 10 weeks (95%CI, 7.1 to 12.8) respectively. Median OS was higher for EGFR mut pts compared to wt pts, 38 weeks (95%IC 13.6-62.4) and 19 weeks (95%IC, 4.06-33.9) respectively, however this difference was not statistically significant (p=0.36) probably due to lack of statistical power.

      table1_lmc.jpg

      Conclusion

      Methotrexate-based IT given concurrently with systemic TKI may confer a higher clinical benefit and a trend toward OS benefit in NSCLC patients with LCM and EGFR activating mutations.

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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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      OA03.03 - Initial Efficacy and Safety Results of Irinotecan Liposome Injection (nal-IRI) in Patients with Small Cell Lung Cancer (Now Available) (ID 1985)

      13:30 - 15:00  |  Author(s): Maria Jove

      • Abstract
      • Presentation
      • Slides

      Background

      SCLC accounts for ~15% of lung cancers, with 5-year survival <10%. 50-90% of patients with extensive disease respond to initial treatment; many rapidly relapse due to acquired resistance to front-line platinum-based chemotherapy. Limited treatment options are available for second-line patients. nal-IRI is a liposomal formulation of irinotecan (topoisomerase-1 inhibitor), utilizing intraliposomal stabilization technology to enable high drug load and in-vivo stability.

      Method

      RESILIENT (NCT03088813) is a two-part Phase 2/3 study assessing the safety, tolerability, and efficacy of monotherapy nal-IRI in SCLC patients who progressed on/after a front-line platinum regimen: Part 1 includes dose-finding then dose-expansion. Key eligibility criteria included ECOG PS 0-1 and adequate organ function, with prior exposure to immunotherapy allowed. Eligible patients received nal-IRI 70mg/m2 or 85mg/m2 (free-base equivalent) q2w. Primary endpoints were safety and tolerability. Efficacy assessments included objective response rate (ORR), best overall response (BOR), progression-free survival (PFS), and overall survival (OS).

      Result

      30 patients were treated for >12 weeks in Part 1 (male, 43%; median age, 60.4y; platinum-resistant, 40%) with tumor assessments q6w. During dose-finding, 5 patients received nal-IRI 85mg/m2 (deemed not tolerable: dose-limiting toxicity) and 12 patients received nal-IRI 70mg/m2 (deemed tolerable: selected for dose expansion). At data cut-off** (median follow-up, 4.4mo), 25 patients had received nal-IRI 70mg/m2. Diarrhea was the most common gastrointestinal adverse events (AEs) (Gr3, 20%). Hematologic AEs included neutropenia (Gr3, 8%; Gr4, 8%), anemia (Gr3, 8%), febrile neutropenia (Gr3, 4%), thrombocytopenia (Gr3, 4%; Gr4, 4%). Preliminary efficacy identified 11 patients with partial responses (ORR 44%), BOR (PR+SD) of 72%, and 12-week disease control rate (DCR12wks PR+SD) of 48%. PFS and OS are not yet mature.

      Conclusion

      Part 1 demonstrated encouraging anti-tumor activity for nal-IRI 70mg/m2 in patients with SCLC (ORR: 44%, BOR: 72%). nal-IRI 70mg/m2 was generally well tolerated. Future research is warranted to assess nal-IRI in second-line SCLC.

      Table 1. Baseline Demographic, Patient Disposition, Safety & Tolerability, and Clinical Efficacy for Part 1 of the RESILIENT study

      Dose-Finding /
      Dose-Exploration Phase
      Irinotecan
      Liposome
      Injection
      85mg/m2
      (N=5)
      Irinotecan
      Liposome
      Injection
      70mg/m2
      (N=25)
      Baseline Characteristics
      Gender, Male, n (%) 3 (60.0) 10 (40.0)
      Age (Years, median) 62.0 59.0
      Baseline ECOG
      0 1 (20.0) 3 (12.0)
      1 4 (80.0) 22 (88.0)
      Time Since Most Recent Progression (Weeks, median) 3.4 3.2
      Disease Location, n (%)
      Locally Advanced 0 2 (8.0)
      Metastatic 5 (100.0) 23 (92.0)
      Disposition, n (%)
      Patient Completed Study 4 (80.0) 12 (48.0)
      Patient Currently Ongoing* 7 (28.0)
      Deaths 2 (40.0) 6 (24.0)
      Disease Related 1 3
      Adverse Event Not Related to Study Drug 1 1
      Cardiac Arrest 1 -
      Hepatic Failure - 1
      Adverse Event Related to Study Drug 0 2
      Abdominal Sepsis - 2
      Patient Discontinued Treatment 5 (100.0) 18 (72.0)
      Safety & Tolerability, n (%)
      Any Treatment-Emergent Adverse Event (TEAE) 5 (100.0) 25 (100.0)
      Grade 3 or Higher TEAE (≥ 2 patients) 5 (100.0) 15 (60.0)
      Neutropenia 1 (20.0) 4 (16.0)
      Anemia 2 (8.0)
      Thrombocytopenia 2 (8.0)
      Diarrhea 3 (60.0) 5 (20.0)
      Asthenia 2 (8.0)
      General Physical Health Deterioration 2 (8.0)
      Pneumonia 2 (40.0) 1 (4.0)
      Abdominal Sepsis 2 (8.0)
      Hypokalemia 1 (20.0) 2 (8.0)
      Renal Failure 2 (8.0)
      Best Overall Response
      Complete Response (CR)
      Partial Response (PR) 2 (40.0) 11 (44.0)
      Stable Disease 1 (20.0) 7 (28.0)
      Progressive Disease 1 (20.0) 5 (20.0)
      Non-evaluable 1 (20.0) 2 (8.0)
      Objective Response Rate
      CR + PR 2 (40.0) 11 (44.0)
      Non-responder 3 (60.0) 14 (56.0)
      ** Data Cut-off: May 8, 2019.
      * Per RECIST v1.1 or RANO criteria.

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