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Brian Henick



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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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      OA03.07 - Immune-Related Adverse Events and Clinical Outcome to Anti PD-1 Axis Inhibition in SCLC: A Multicenter Retrospective Analysis (Now Available) (ID 2880)

      13:30 - 15:00  |  Author(s): Brian Henick

      • Abstract
      • Presentation
      • Slides

      Background

      Immune-checkpoint inhibitors (ICIs) have shown promising activity in only a fraction of patients with small cell lung cancer (SCLC), and factors associated with clinical benefit are not well characterized. The development of immune-related adverse events (irAEs) may correlate with benefit from immune checkpoint inhibitors (ICIs) among patients with cancer. Whether an association exists between irAE development and improved clinical outcomes to ICIs in small cell lung cancer (SCLC) is unknown.

      Method

      We retrospectively analyzed data from five participating academic centers: the Dana-Farber Cancer Institute, East Carolina University, Columbia University, Beth Israel Deaconess Medical Center, and Johns Hopkins University. Patients with SCLC who received at least one dose of a programmed death (ligand) PD-(L)1 inhibitor alone or in combination with a cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitor were included in this study. To account for the time-dependent nature of irAE onset and clinical benefit from immunotherapy, we identified patients with early irAEs (defined as those occurring within 6 weeks of ICI treatment initiation) and performed a landmark analysis at this time point.

      Result

      Among 157 patients treated with ICIs, 65 (41.4%) experienced at least one irAE. Median time to the first irAE onset was 28 days (IQR:15-56). Baseline clinicopathologic characteristics were well balanced between patients who developed irAEs and those who did not. Median tumor mutational burden (TMB) was significantly higher among patients with irAEs compared to those without (14.4 vs 8.4 mutations/megabase [mut/Mb], P <0.01). Patients who developed at least one irAE had a significantly higher objective response rate (26.3% versus 3.3%, P <0.001), and significantly longer median progression-free survival (mPFS, 4.1 vs 1.3 months, HR: 0.30 [0.20-0.43, P <0.001]) and median overall survival (mOS, 14.1 vs 2.9 months, HR: 0.32 [0.21-0.48], P <0.001). The proportion of patients who were progression-free at 6, 9, and 12 weeks was significantly higher in patients who developed early irAEs compared to those who did not develop early irAEs (6 weeks: 89.5% vs 69.5%, P =0.01; 9 weeks: 71.1% vs 40%, P =0.001; 12 weeks: 65.8% vs. 31.6%, P <0.001). The median TMB was also significantly higher in patients who developed early irAEs (14.5 vs 8.7 mut/Mb, P <0.01).

      Conclusion

      Patients with SCLC treated with ICIs who developed early irAEs had a higher TMB and enhanced antitumor responses compared to those who did not develop irAEs. Whether a higher TMB is associated with the development of irAEs remains to be determined mechanistically.

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