Examining the use of PD-L1 and tTMB in the CASPIAN Trial

Author(s):

Ticiana A. Leal, MDAnne Chiang, MD, PhD, Yale School of Medicine Smilow Cancer Hospital

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.

EP: 1.Optimizing First-Line Therapy for Limited-Stage Small Cell Lung Cancer

EP: 2.ADRIATIC Trial: Durvalumab, cCRT Timing, and Survival in LS-SCLC

EP: 3.cCRT-to-Durvalumab Interval in Limited Stage LS-SCLC

EP: 4.Examining 3-Year Update Data from the CASPIAN Trial

EP: 5.Predictors of Immunotherapy Response in Limited and Extensive SCLC

EP: 6.Overcoming Immunotherapy Resistance in Small Cell Lung Cancer

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EP: 7.Examining the use of PD-L1 and tTMB in the CASPIAN Trial

EP: 8.Redefining SCLC: Molecular Subtypes and Blood Biomarkers Guide Therapy

EP: 9.Navigating Later-Line Therapy Sequencing in LS-SCLC Progression

EP: 10.DELLphi-301: Platinum Chemotherapy Efficacy in SCLC Survival

EP: 11.Reviewing Ideate-Lung02: Durable Responses in Advanced SCLC

EP: 12.Examining Key Data from DAREON-8

EP: 13.Closing Thoughts and Key Takeaways on Small Cell Lung Cancer

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.)
1. Importance or non-importance of PD-L1 and tissue TMB in predicting PFS and ORR.
2. The potential OS benefit of adding tremelimumab to durvalumab + EP in patients with a PD-L1 expression of >1%.
3. [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?
1. How might ctDNA methylation overcome the limitations of tissue-based biomarker assessment in better classifying both transcription factor-driven and independent SCLC subtypes?
2. 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.
1. Epithelial mesenchymal transition (EMT) status
2. Expression of: T cell attractant chemokines CCL5 and CXCL10
3. CD8A and CD8B, which suggests greater cytotoxic T cell infiltration and cytolytic activity
4. Interferon-γ related T cell gene expression profile (GEP)
5. Bruton’s tyrosine kinase