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Mark Doherty



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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
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      P1.01-39 - Is There an Association Between Intracranial Progression and Overall Survival or Neurologic Death in Patients with EGFR Positive NSCLC? (ID 727)

      09:45 - 18:00  |  Presenting Author(s): Mark Doherty

      • Abstract

      Background

      Many studies have examined the incidence of Brain Metastases (BrM) in EGFRm+ NSCLC, and their impact on radiographic and survival outcomes. We have examined the incidence of ND and predictive factors in a retrospective cohort. The clinical significance of ICP remains controversial; patients who develop new lesions may be treated with further locoregional treatment such as stereotactic radiosurgery (SRS). This study examines the association between ICP and survival or ND, to help define appropriate endpoints for future trials.

      Method

      All patients treated for BrM from EGFRm+ NSCLC between 2004 and 2016 were identified from an institutional registry. Clinical data regarding demographics, progression events, pattern of progression, and treatment were extracted from medical records and verified with imaging reports. A multivariable competing-risks model was constructed to test the association between ICP at 6, 12 and 18 months and the outcome of ND. A separate model tested the association between ICP and OS.

      Result

      198 patients were included in the study. Median age was 61 years, 67% of patients were female, 46% had BrM at NSCLC diagnosis. Median DS-GPA was 2.5. Median OS for the group was 20 months, and the 5-year cumulative incidence of neurologic death was 40%. 111 patients (56%) had ICP and median intracranial PFS was 16 months; 29% had ICP within 6 months and 33% between 6 and 12 months, 18% at 12-18 months and 21% at >18 months. ICP was due to new BrM in 51%, progression of existing BrM in 34% and leptomeningeal carcinomatosis in 15%. Among patients with ICP, earlier progression was associated with ND (HR 2.48, p=0.01, see table). In addition, pattern of ICP was significant; patients with leptomeningeal spread (HR 3.74, p<.001) had higher risk of ND than those with new BrM or progression of existing lesions. In a multivariable model, early ICP, pattern of ICP and more initial BrM were independently associated with higher risk of ND and also shorter OS.

      Regression models of ND and OS

      Univariate Model of Neurologic Death

      Multivariable Model of Neurologic Death

      Multivariable Model of Overall Survival

      Covariate

      HR (95% CI)

      P value

      HR (95% CI)

      P value

      HR (95% CI)

      P value

      Intracranial Progression

      < 6 months

      6-12 months

      12-18 months

      >18 months

      2.48 (1.21-5.08)

      1.56 (0.75-3.23)

      1.61 (0.72-3.57)

      ref

      0.013

      0.24

      0.25

      4.88 (2.13-11.19)

      2.69 (1.06-6.80)

      3.85 (1.44-10.29)

      ref

      <.001

      0.036

      0.007

      11.22 (5.11-24.64)

      5.31 (2.47-11.42)

      4.82 (2.16-10.77)

      ref

      <.001

      <.001

      <.001

      Pattern of Progression

      New lesion

      Progression of existing BrM

      Leptomeningeal Spread

      ref

      1.29 (0.70-2.35)

      3.74 (1.96-7.15)

      0.41

      <.001

      ref

      1.12 (0.55-2.26)

      4.70 (2.11-10.48)

      0.76

      <.001

      ref

      1.54 (0.93-2.57)

      3.19 (1.64-6.20)

      0.10

      <.001

      Number of Initial BrM

      1-4

      5-10

      >10

      ref

      1.92 (0.95-3.86)

      2.94 (1.60-5.39)

      0.07

      <.001

      ref

      2.43 (1.05-5.62)

      2.57 (1.11-5.90)

      0.038

      0.027

      ref

      3.27 (1.61-6.62)

      3.74 (1.96-7.15)

      0.001

      <.001

      First Line CNS Treatment

      WBRT

      SRS

      Systemic alone

      Ref

      0.69 (0.38-1.24)

      0.58 (0.27-1.23)

      0.22

      0.15

      Ref

      1.17 (0.49-2.75)

      0.88 (0.42-1.87)

      0.73

      0.88

      Ref

      1.10 (0.57-2.11)

      1.28 (0.70-2.34)

      0.79

      0.43

      EGFR Exon 19 vs 21

      0.73 (0.44-1.23)

      0.24

      0.71 (0.40-1.24)

      0.23

      0.72 (0.52-1.00)

      0.05

      BrM at Diagnosis

      0.93 (0.54-1.60)

      0.78

      1.45 (0.77-2.73)

      0.26

      0.93 (0.65-1.32)

      0.69

      Conclusion

      Among patients with brain metastases from EGFRm+ NSCLC, shorter time to intracranial progression was associated with higher rates of neurologic death, as was the pattern of progression. This supports the validity of studies using intracranial progression as an endpoint, particularly if pattern of disease is taken into account.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-72 - Safety of Palliative Radiotherapy and Immune Checkpoint Inhibitors in Patients with Metastatic Non-Small Cell Lung Cancer (ID 2638)

      10:15 - 18:15  |  Author(s): Mark Doherty

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) are now widely used as standard of care treatments for metastatic non-small cell lung cancer (m-NSCLC) alongside palliative radiotherapy (RT). Commonly used ICIs have long half-lives, typically between 3-4 weeks, and with reported effect even months after discontinuation. The safety of RT based on timing and biologically effective dose (BED) with respect to ICIs is not yet elucidated. This study hypothesized that RT use within 3 months interval prior and after ICI does not increase grade ≥2 toxicities from either ICIs or RT.

      Method

      This retrospective analysis includes m-NSCLC patients treated with both RT and ICIs at the Sunnybrook Odette Cancer Centre, Toronto from June 2014 to January 2019. Patients were identified by both our chemotherapy computerized physician order entry system, OPIS and radiation database. ICIs and RT-related toxicities after first ICIs dose were graded as per CTCAE v4.0. Based on timing and location, toxicities attributed to either ICIs or RT by clinicians.

      Result

      Forty-four m-NSCLC patients treated with ICIs (nivolumab, pembrolizumab, or atezolizumab) and RT were identified. Twenty one (47.7%) were females, median age 67.5 (33.4- 83.2) years, 36 (81.8%) Caucasian, 42 (95.5%) non-squamous histology, 34 (77.3%) previous or current smokers, PD-L1 1-49% in 7 (15.9%) patients and ≥50% in 15 (34.1%), 9 (20.5%) EGFR/ALK positive, 40 (90.9%) ECOG 0-1. Median follow-up was 10.6 (0.7- 54.6) months. Twenty-five patients (group 1) received RT within 3 months prior and after ICIs (60 courses total, 32 (53.3%) extracranial), with median biologically effective dose with α/β= 10 (BED10) 59.5 (14.4-72.0) Gy10, while 19 had no RT in that interval (group 2). Overall, group 1 had 142 RTs (82 outside interval), with median BED10 52.7 (14.4-120) Gy10, while group 2 had 51 RTs, with median BED10 52.8 (10.1-105.6) Gy10. Grade ≥2 toxicities (8 total, 7 ICIs-related, 1 RT-related) occurred in 7 (28.0%) patients from group 1, and in 4 patients (26.3%) in group 2 (6 total all ICIs-related); this was not statistically significant (χ2 p= 0.60). Five grade 3 toxicities were: pneumonitis (2), hepatitis (1), colitis (1), and nausea (1). No grade 4 or 5 toxicity was reported.

      Conclusion

      Palliative RT within 3 months of ICIs did not increase ICIs and RT-induced grade ≥2 toxicities. Proceeding with ICIs while receiving palliative RT for m-NSCLC is likely safe. Further research incorporating larger cohort is planned to verify these safety results.

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