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A.E. Adeni



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-055 - Spectrum of Early Progression in Advanced NSCLC Patients Treated with PD-1 Inhibitors: Identifying Markers for Poor Outcome (ID 8275)

      09:30 - 09:30  |  Author(s): A.E. Adeni

      • Abstract

      Background:
      While marked responses have been observed in patients with non-small-cell lung cancer (NSCLC) treated with PD-1 pathway inhibitors, anecdotal evidence indicates that rapid progression with dramatic tumor burden increase early in the course of therapy may be noted in a few patients. The study characterized the spectrum of early progression of advanced NSCLC treated with PD-1 inhibitors, and investigated quantitative imaging markers for poorer outcome.

      Method:
      The study included 134 patients (53 men, 81 women; median age: 66) with advanced NSCLC treated with commercially prescribed single-agent nivolumab or pembrolizumab, who had follow-up CT scans at 8 +/- 2 weeks of therapy. Tumor burden measurements were performed using RECIST1.1 on baseline and 8-week scans to characterize the spectrum of early progression during PD-1 therapy. Tumor burden changes at 8 weeks were studied for association with overall survival (OS), which was measured from the 8-week scan date.

      Result:
      The tumor burden changes at 8 weeks comparing to baseline ranged from -72.7% to +138.7% (median: +4.3%; the 90[th] percentile: +50.07%). OS of 15 patients with ≥50% increase of tumor burden at 8 weeks was significantly shorter compared to 119 patients with <50% increase at 8 weeks (median OS: 4.5 months [95%CI: 1.3-4.9] vs. 12.7 months [95%CI: 8.5-14.7]; log-rank p=0.0003). Among 42 patients who experienced tumor burden increase ≥20% (RECIST progression threshold) at 8 weeks, 15 patients with ≥50% increase had shorter OS than 27 patients with ≥20% but <50% increase (median OS: 4.5 months [95%CI: 1.3-4.9] vs. 6.8 months [95%CI: 5.4-20.1]; log-rank p=0.08), indicating that ≥50% increase threshold may identify a distinct group of early progressors with poorer prognosis. Never smokers were more likely to experience ≥50% increase at 8 weeks than former or current smokers (Fisher p=0.03).

      Conclusion:
      Tumor burden increase of ≥50% at 8 weeks of therapy was associated with significantly shorter OS in advanced NSCLC patients treated with commercial PD-1 inhibitors, indicating that it can serve as an imaging marker to identify a distinct subset of patients with poorer outcome of PD-1 inhibitor therapy, and may thus help guide treatment decisions.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-002 - Drug-Related Pneumonitis in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Commercial PD-1 Inhibitors (ID 7559)

      09:30 - 09:30  |  Author(s): A.E. Adeni

      • Abstract

      Background:
      PD-1 inhibitor-related pneumonitis is recognized as a serious immune-related adverse event especially among NSCLC patients. The study investigated the radiographic patterns, clinical course, and risk factors of pneumonitis in advanced NSCLC patients treated with commercial PD-1 inhibitors.

      Method:
      The study included 210 patients (93 men, 117 women; median age: 65) with advanced NSCLC treated with commercially prescribed single-agent nivolumab or pembrolizumab. Chest CT scans during therapy were reviewed for abnormalities suspicious for pneumonitis by an independent review of two radiologists. Radiographic patterns of pneumonitis were classified using the ATS/ERS classification of interstitial pneumonia.

      Result:
      Pneumonitis was radiographically detected in 20 patients (20/210; 9.5%). Median time from the initiation of therapy to pneumonitis was 7.8 weeks. The radiographic pattern of pneumonitis was a cryptogenic organizing pneumonia (COP) pattern in 18, a non-specific interstitial pneumonia (NSIP) pattern in one, and a hypersensitivity pneumonitis (HP) pattern in one patient. Fifteen patients (75%) were symptomatic and 5 patients (25%) were asymptomatic with radiographic abnormalities alone. PD-1 inhibitors were held in 17 patients (85%), and corticosteroids were given in 12 patients (60%). Seven patients were hospitalized for treatment of pneumonitis. Three patients were re-treated with PD-1 inhibitors and two developed recurrent pneumonitis. There were no significant differences in clinical characteristics between patients with and without pneumonitis (p>0.34). Figure 1



      Conclusion:
      PD-1 inhibitor-related pneumonitis was noted in 9.5% of the advanced NSCLC patients treated with commercially prescribed PD-1 inhibitors. Radiographic pattern of pneumonitis was most commonly a COP pattern. Recurrent pneumonitis was common among those who were re-treated with PD-1 inhibitors. Further studies are necessary to identify risk factors for pneumonitis.