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Sanja Dacic
Moderator of
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MS 18 - Biomarker for Anti-PD-L1 Therapy (ID 540)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Immunology and Immunotherapy
- Presentations: 5
- Moderators:Yuichi Ishikawa, Sanja Dacic
- Coordinates: 10/17/2017, 15:45 - 17:30, Main Hall
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MS 18.02 - An Update on the BLUEPRINT and Related Projects (ID 8123)
15:45 - 17:30 | Presenting Author(s): Fred R. Hirsch
- Abstract
- Presentation
Abstract not provided
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MS 18.03 - Potential Application of Molecular Genomic for Immunotherapy (ID 7645)
15:45 - 17:30 | Presenting Author(s): Rolf A Stahel
- Abstract
- Presentation
Abstract not provided
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MS 18.04 - PD-L1 Expression in Early Stage Lung Cancer (ID 7646)
15:45 - 17:30 | Presenting Author(s): Jin-Haeng Chung
- Abstract
- Presentation
Abstract:
The significant activity of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors in heavily pre-treated patients with advanced non–small-cell lung cancer (NSCLC) marked the beginning of a new era of immunotherapy. Recently published randomised clinical trials’ data have led to the approval of 3 PD-1/PD-L1 inhibitors—nivolumab (Opdivo; Bristol-Myers Squibb Company), pembrolizumab (Keytruda; Merck Sharp & Dohme Corp), and atezolizumab (Tecentriq, Genentech/Roche)—for the treatment of advanced NSCLC after first-line therapy. Furthermore, pembrolizumab was recently approved by the FDA as a first-line therapy for patients with advanced NSCLC. However, the overall response rates to these agents in an unselected population are reportedly low, thus emphasising the need for predictive biomarkers that identify beneficial candidates. The recently approved tests for anti-PD-1/PD-L1 therapy in NSCLC include the assessment of PD-L1 expression using immunohistochemistry (IHC) as a companion diagnostic test (22C3 for pembrolizumab) and 2 complementary diagnostic tests (28-8 for nivolumab and SP142 for atezolizumab). Another PD-L1 assay is being currently tested in clinical trials (e.g. SP263). In addition to commercial assays, laboratories and research institutions may establish their own laboratory-developed tests (LDTs) using various antibodies available, most notably the E1L3N clone. Hence, the PD-L1 expression status, as well as its predictive and prognostic value, differ considerably based on the antibody clones, platforms, and interpretation criteria used. However, the current assays evaluating the predictive role of tumour PD-L1 expression remain without harmonization in terms of the staining analysis and scoring system. The intratumoural heterogeneity in PD-L1 expression is another important issue. At present, PD-L1 testing is mainly conducted on biopsy specimens, which may not represent the tumour as a whole, and it may lead to false results, particularly in cases where testing is conducted using small tissue specimens, such as bronchial or transthoracic biopsy specimens. The resulting false-negative results could lead to the under-treatment of patients. In this presentation, I’d like to introduce 1) the results of comparison study between 4 different PD-L1 IHC and scoring systems in the surgically resected early stage lung cancer specimen 2) the correlation of PD-L1 expression between TMA specimens and the corresponding resected specimen to better understand the intratumoral heterogeneity.
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MS 18.05 - Liquid Biopsy Biomarkers in IO: Is There Room? (ID 7647)
15:45 - 17:30 | Presenting Author(s): Christian Rolfo
- Abstract
- Presentation
Abstract not provided
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MS 18.06 - Future Perspectives of Biomarkers for Anti PD-1/PD-L1 Therapy (ID 8124)
15:45 - 17:30 | Presenting Author(s): Julie R Brahmer
- Abstract
- Presentation
Abstract not provided
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Author of
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-047 - Comparison of PD-L1 Immunohistochemistry Assays and Response to PD-L1 Inhibitors (ID 10278)
09:30 - 16:00 | Presenting Author(s): Sanja Dacic
- Abstract
Background:
The FDA has approved different companion and complementary PD-L1 assays for selection of patients for different PD-L1 inhibitors. As a result, laboratories intending to implement FDA approved assays face significant operating and capital expenses. Several studies have demonstrated technical concordance between different PD-L1 assays, but their clinical validity in terms of the response to treatment has not entirely been explored. The aim of our study is to prospectively assess the staining performance of laboratory developed tests (LDT) for Ventana SP263 (nivolumab) and Dako 22C3 (pembrolizumab) clones on formalin fixed paraffin embedded samples, and to investigate the association between PD-L1 assays and response to PD-L1 inhibitors.
Method:
189 sequential lung tumor samples from patients with advanced NSCLC were prospectively stained with Ventana SP263 and Dako 22C3 clones. Both antibodies were optimized for use on the automated Ventana BenchMark ULTRA platform, and validated against corresponding FDA approved assays. Scoring algorithms for staining of the tumor cells approved by matched FDA assays were applied to all samples. Best overall response (BOR) for 43 patients treated with either nivolumab or pembrolizumab were assessed using RECIST v.1.1 and correlated with PD-L1 expression with SP263 and 22C3 using cut off points of 1%, 5% and 10%, 1-49% and 50%.
Result:
Ventana SP263 and Dako 22C3 LDTs showed good agreement with a concordance correlation coefficient of 0.86 (95% CI 0.82-0.90). Comparing the assays using the cutoffs of 1%, 5% or 10% for SP263 and the two cutoffs of 1% and 50% for 22C3 showed an association between the two assays as well (p<0.0001). There were no differences in BOR between pembrolizumab and nivolumab (p=0.12). For SP263, BOR was associated with a cut off point of 10% (Fisher’s p=0.030); while the 1% (Fisher’s p=0.09)and 5 % (Fisher’s p=0.054) cut off points were not associated with response. In contrast, for 22C3, BOR was associated with a cut off point of 1% (Fisher’s exact test p-value = 0.006), 5% (p 0.006) and 10% (0.006)
Conclusion:
Similar to FDA approved assays, Ventana SP263 and Dako 22C3 LDT, if properly validated, demonstrate good concordance, but are not interchangeable. Dako 22C3 is more sensitive assay and its expression shows better association with therapeutic response. Larger studies evaluating associations of alternative staining assays and a response to specific therapy are needed.
