ASCO 2024: Immunotherapy for the Treatment of Small Cell Lung Cancer - Episode 7
Examining the use of PD-L1 and tTMB in the CASPIAN Trial
Key opinion leaders examine the PD-L1 expression and tissue tumor mutational burden (TMB) data from the CASPIAN trial, which evaluated the combination of durvalumab with platinum-etoposide for extensive-stage small cell lung cancer (ES-SCLC), weighing the potential predictive value of PD-L1 and tissue TMB in assessing progression-free survival (PFS) and objective response rate (ORR) outcomes.
- Please discuss the PD-L1 expression and tissue TMB data from the CASPIAN trial evaluating durvalumab + platinum-etoposide for extensive-stage small cell lung cancer(ES-SCLC). (Paz-Ares L, et al. Clin Cancer Res. 2024; 30:824-835.)
- Importance or non-importance of PD-L1 and tissue TMB in predicting PFS and ORR.
- The potential OS benefit of adding tremelimumab to durvalumab + EP in patients with a PD-L1 expression of >1%.
- [Q4W vs single dose tremelimumab]
- In your expert opinion, is there value in combining the tTMB score and PD-L1 expression level as predictive biomarkers of therapeutic response?
- How might ctDNA methylation overcome the limitations of tissue-based biomarker assessment in better classifying both transcription factor-driven and independent SCLC subtypes?
- How could further refinement of this technique facilitate the initial diagnosis of SCLC, rapid therapy initiation, and liquid-biopsy-guided surveillance throughout treatment?
- Please elaborate on how aspects of an inflamed, tumor microenvironment might foster greater therapeutic response to immune checkpoint blockade.
- Epithelial mesenchymal transition (EMT) status
- Expression of: T cell attractant chemokines CCL5 and CXCL10
- CD8A and CD8B, which suggests greater cytotoxic T cell infiltration and cytolytic activity
- Interferon-γ related T cell gene expression profile (GEP)
- Bruton’s tyrosine kinase
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