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Vashine Kamesan
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-21 - The Utility of PD-L1/CD8 Dual Immunohistochemistry for Prediction of Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) (ID 13815)
16:45 - 18:00 | Author(s): Vashine Kamesan
- Abstract
Background
PD-L1 immunohistochemistry (IHC) is an important predictive biomarker for PD-(L)1 blockade in advanced non-small cell lung cancer (NSCLC); however, this assay is imperfect. The presence of CD8+ tumor infiltrating lymphocytes (TILs) may be a complimentary biomarker for response to immunotherapy. Thus, we examined the performance of PD-L1/CD8 dual IHC (dIHC) in two cohorts of NSCLC patients receiving immunotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients were identified through retrospective review of medical oncology and pathology databases. The first cohort predominantly received nivolumab as a 2nd or later line treatment; tissue samples were mainly obtained at initial diagnosis. The second cohort received pembrolizumab as a first line therapy, and tissue samples were procured immediately before the initiation of immunotherapy. PD-L1/CD8 dIHC was performed on those tissue samples. Percentage of tumor cells with membranous PD-L1 expression and CD8+ stromal cells were measured, and CD8+ TILs were semi-quantitatively evaluated. The quantities of CD8+ T cells were dichotomized with appropriate cut-offs.
4c3880bb027f159e801041b1021e88e8 Result
Eighty-four patients were identified, including 60 in the Nivolumab cohort (NC) and 24 in the Pembrolizumab cohort (PC). In the NC, PD-L1 expression ≥1% was marginally associated with improved progression-free survival (PFS, p=0.09), and an increased rate of response (p=0.08). CD8+ TILs and stromal cells did not correlate with outcome. However, a subset of PD-L1-positive patients who showed abundant CD8+ TILs and stromal cells had significantly reduced PFS (p=0.04). In the PC cohort, all cases chosen exhibited PD-L1 expression in ≥50% of tumor cells. Increased CD8+ TILs were correlated with improved PFS, (p=0.0194), and an increase in both CD8+ TILs and stromal cells was also associated with improved PFS (p= 0.0238).
8eea62084ca7e541d918e823422bd82e Conclusion
Although limited by small sample size, this study suggests that PD-L1/CD8 dIHC improves the prediction of response to the PD-1/PD-L1 blockade in advanced NSCLC patients when it is performed on tissue samples obtained immediately before the initiation of the blockade as first-line therapy . However, for the 2nd or later line of treatment, dIHC on archival tissue samples obtained before initial therapy provides a useful but less clear picture of the tumor immune microenvironment. Reduced PFS seen in patients with PD-L1 expression and abundant CD8+ TILs and stromal cells may be due to T-cell exhaustion after the chemotherapy before the PD-1/PD-L1 blockade. These findings suggest that PD-L1/CD8 dIHC may be useful for treatment response stratification in advanced lung cancer patients.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.12-02 - Dynamics of DLL3 and ASCL1 Expression in SCLC Over Disease Course (ID 12609)
12:00 - 13:30 | Author(s): Vashine Kamesan
- Abstract
Background
SCLC is a high-grade neuroendocrine malignancy highly responsive to first-line therapy, etoposide plus platinum (EP), but increasingly resistant to subsequent lines of therapy. Because SCLC is rarely biopsied following the initial diagnosis, the dynamics of expression of therapeutically relevant biomarkers in relapsed disease are poorly understood. ASCL1 is an oncogenic driver of SCLC and directs transcription of delta-like protein 3 (DLL3), an atypical Notch receptor family ligand involved in neuroendocrine tumorigenesis and the target of the antibody drug conjugate rovalpituzumab tesirine (Rova-T™). We investigated ASCL1 and DLL3 expression in SCLC patient (pt) tumor biopsies and patient-derived xenografts (PDXs) collected serially from time of diagnosis (pre-treatment) and after progression following ≥1 lines of therapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
Fresh cut, formalin fixed, paraffin embedded tissue from primary SCLC tumors and PDXs was sectioned and stained with mouse monoclonal antibodies against DLL3 (SC16.65) and ASCL1 (SC72.201) on the Dako platform. ASCL1 and DLL3 expression were scored as a percent of positive cells and correlated with each pt’s treatment history.
4c3880bb027f159e801041b1021e88e8 Result
Among biopsies and/or PDXs derived over serial time points, 6 cases had baseline positive DLL3 expression ranging from 15-80% of cells with a mean of 50% pre-EP. All 6 remained positive following progression after EP, with DLL3 expression ranging from 10-100% of cells with a mean of 66%. Up to 7 serial tissue or PDX samples were available over the course of multiple treatments for 2 pts, and DLL3 and ASCL1 expression remained consistent over time, being strongly positive in 1 case and negative in the other. Among biopsies and PDXs established at matched time points, ASCL1 and DLL3 expression were consistent in 7/7 and 7/8 cases, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
ASCL1 and DLL3 expression remain mostly consistent pre- and post- chemotherapy in pts with SCLC, suggesting that expression of these biomarkers in archival tissue likely accurately estimates expression even after intervening treatments. Furthermore, PDXs derived both from biopsies and circulating tumor cells maintain ASCL1 and DLL3 expression that reflects the pt tumor, supporting use of PDXs to model pt tumor biology.
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