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M. Altan
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-046 - Quantitative Measurement of B7-H3 Protein Expression and Its Association with B7-H4, PD-L1 and TILs in NSCLC (ID 4288)
14:30 - 14:30 | Author(s): M. Altan
- Abstract
Background:
B7-H3 (CD276) is a type I transmembrane protein that belongs to the B7 immunoregulatory family including PD-L1 (B7-H1) and is upregulated in multiple malignancies including Non-Small Cell Lung Cancer (NSCLC). Clinical activity of monoclonal B7-H3 blocking antibodies such as Enoblituzumab are under investigation. In this study we measured the levels of B7-H3 protein in NSCLC and studied its association with major tumor infiltrating lymphocyte (TIL) subsets, levels of PD-L1, B7-H4 and clinico-pathological characteristics in three independent NSCLC cohorts.
Methods:
We used automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3 (clone D9M2L, CST), PD-L1 (clone SP142, Spring), B7-H4 (Clone D1M8I, CST) CD3, CD8 and CD20 in 634 NSCLC cases from 3 retrospective cohorts represented in tissue microarray format. The targets were selectively measured in the tumor and stromal compartments using co-localization with cytokeratin. Associations between the marker levels, major clinic-pathological variables and survival were analyzed.
Results:
Expression of B7-H3 protein was found in 80.4% (510/634) of the cases and the levels were higher in the tumor than in the stromal compartment. High B7-H3 protein expression level (top 10 percentile) was associated with poor survival in two out of three of the cohorts (p <0.05). Elevated B7-H3 was consistently associated with smoking history across the 3 cohorts, but not with sex, age, clinical stage and histology. Co-expression of B7-H3 and PD-L1 was found in 17.6% of the cases (112/634) and with B7-H4 in 10% (63/634). B7-H4 and PD-L1 were simultaneously detected only in 1.8% of NSCLCs (12/634). The expression of B7-H3 was not associated with the levels of CD3, CD8 and CD20 positive TILs.
Conclusion:
B7-H3 protein is expressed in the majority of NSCLCs and is associated with smoking history. High B7-H3 protein levels may have a prognostic effect in lung carcinomas. Elevated levels of B7-H3 are not associated with lymphocyte infiltration. Co-expression of B7-H3 with PD-L1 and B7-H4 is relatively low, suggesting a non-redundant biological role of these targets and possibilities for combination therapies using monoclonal antibodies.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-048 - A Phase I/II Trial Evaluating the Combination of Stereotactic Body Radiotherapy and Pembrolizumab in Metastatic NSCLC (ID 5249)
14:30 - 14:30 | Author(s): M. Altan
- Abstract
Background:
Immune checkpoint inhibitors are taking on a growing role in the treatment of patients with metastatic NSCLC. Pre-clinical evidence suggests that radiotherapy may increase the frequency, or enhance the strength of the host anti-cancer immune response. We report the preliminary results of an ongoing phase I/II trial combining stereotactic body radiotherapy (SBRT) and the anti-PD-1 antibody pembrolizumab in patients with metastatic NSCLC.
Methods:
Eligible patients are those with metastatic NSCLC who have received no prior immune-directed therapy, and have at least 2 sites of measurable disease as per RECIST 1.1. PD-L1 expression is not required for study entry. All patients are treated with pembrolizumab at 200 mg every 3 weeks until development of progressive disease by immune-related RECIST criteria (irPD). After irPD, patients receive SBRT to a single site of disease and continue pembrolizumab. The primary endpoint is safety and tolerability. Secondary endpoints include the pre- and post-SBRT overall response rate.
Results:
27 patients with advanced NSCLC have enrolled and started trial therapy. The overall response rate (irPR and irCR) to the initial course of pembrolizumab is 35%. To date, 13 patients have had irPD: 5 were not eligible for SBRT and stopped study treatment (2 developed new brain metastases, 3 had decline in PS), and 8 patients received SBRT to a single site of disease (6 thoracic, 1 adrenal, 1 vertebral) and continued pembrolizumab. 5 of these patients are evaluable for post-SBRT response: 1 patient had confirmed irPD, 4 have irSD and continue pembrolizumab post-SBRT at a median duration of 3 months (range 1 to 5 months). 2 of the 4 patients with irSD have had > 20% decrease in the sum of diameters of their unirradiated targets, since SBRT. Regarding adverse events, in the pre-SBRT phase 6 of 27 patients (22%) developed grade 3 treatment-related toxicity (2 colitis, hepatitis, pneumonitis, hypothyroidism, conjunctivitis). In the SBRT and post-SBRT phases, there have been no grade 2 or greater treatment-related events.
Conclusion:
The addition of SBRT to pembrolizumab has not resulted in an increase in treatment-related toxicity. Several patients who had serially confirmed irPD to pembrolizumab monotherapy underwent SBRT and now have irSD, with some evidence of tumor regression. Updated results will be presented.
