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K. Tanaka
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-010 - Peripheral Blood Biomarkers Associated with Clinical Outcome in Non–Small Cell Lung Cancer Patients Treated with Nivolumab (ID 8547)
09:30 - 09:30 | Author(s): K. Tanaka
- Abstract
Background:
Targeting of the immune system has been found to confer clinical benefit for patients with some types of advanced solid tumor. Given that only a limited number of patients experience a durable response, whereas all those treated are at risk for specific immune side effects, the identification of individuals who are most likely to benefit from nivolumab and similar agents is an important clinical goal. We have now examined the possible impact of clinical parameters determined in the routine laboratory setting—including peripheral blood cell counts such as ANC, absolute lymphocyte count (ALC), absolute monocyte count (AMC), and absolute eosinophil count (AEC)—on outcome in patients with advanced or recurrent NSCLC treated with nivolumab.
Method:
A total of 134 patients with advanced or recurrent NSCLC treated with nivolumab was analyzed retrospectively. Univariable and multivariable analyses were performed to evaluate the relation between survival and peripheral blood parameters measured before treatment initiation, including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count, and absolute eosinophil count (AEC) as well as serum C-reactive protein and lactate dehydrogenase levels. Progression-free survival (PFS), overall survival (OS), and response rate were determined. We further evaluated the association of these factors and the expression level of PD-L1 of tumor tissue.
Result:
Among variables selected by univariable analysis, a low ANC, high ALC, and high AEC were significantly and independently associated with both better PFS (P = 0.001, P = 0.04, and P = 0.02, respectively) and better OS (P = 0.02, P = 0.04, and P = 0.003, respectively) in multivariable analysis. Categorization of patients according to the number of favorable factors revealed that those with only one factor had a significantly worse outcome compared with those with two or three factors. Median PFS was 209, 87, and 42 days and the response rate was 43.5%, 27.1%, and 5.9% in patients with three, two, or one of the three favorable factors, respectively. The association between survival factors and the expresssion of PD-L1 in tumor tissue will be presented at the conference as well.
Conclusion:
A baseline signature of a low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab treatment, with the number of favorable factors identifying subgroups of patients differing in survival and response rate.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-021 - A Checkpoint Molecule B7-H3 as a Novel Immune Therapy Target for Non-Small Cell Lung Cancer (NSCLC) (ID 8598)
09:30 - 09:30 | Author(s): K. Tanaka
- Abstract
Background:
Anti-PD-1 immune therapy improved survival in NSCLC, whereas some patients were not responding to this treatment, indicating the requirement of alternative strategies for these patients. B7-H3, an immune checkpoint molecule, has known to be expressed in some cancer cells including NSCLC. In this study, we examined the therapeutic potential of targeting B7-H3 using a mouse model, also elucidated the expression levels of B7-H3 on NSCLC tumor cells.
Method:
Pan02 murine cancer cells were inoculated in syngeneic mice, and anti-tumor efficacy of anti-B7-H3, anti-PD-L1 antibodies were evaluated. T-cell expression of IFN gamma was evaluated in the spleen and tumor infiltrating lymphocytes using flow-cytometer. B7-H3 expression on tumor cells in patients with NSCLC (n=69) was evaluated by immunohistochemistry.
Result:
In the mouse model study, the treatment with anti-B7-H3 antibody significantly prevented the tumor-growth as compared to isotype antibody. The numbers of CD4+ and CD8+ T-cells infiltrated in the tumor significantly increased following treatment with anti-B7-H3 antibody. Importantly, depletion of CD8+ T-cells cancelled the anti-tumor effect of anti-B7-H3 antibody treatment, indicating that the blockade of B7-H3 potentiates anti-tumor CD8+ T-cell responses. In fact, CD8+ T-cell expressions of IFN gamma in response to tumor cells were improved when mice were treated with anti-B7-H3 antibody. Furthermore, combination with anti-B7-H3 and anti-PD-L1 antibody treatment showed synergic effect in inhibiting tumor-growth. The expressions of B7-H3 were evident on NSCLC tumors, which consists 62% of NSCLC patients.
Conclusion:
Anti-B7-H3 antibody exhibited CD8+ T-cell-mediated anti-tumor effects in the mouse model study. B7-H3 was aberrantly expressed in NSCLC tumor cells. Anti-B7-H3 antibody or its combination with anti-PD-1 antibody is suggested to be effective for patients with NSCLC. Figure 1
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-088a - Phase II Study of Nab-Paclitaxel in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer: SNIPER Study (ID 9803)
09:30 - 09:30 | Author(s): K. Tanaka
- Abstract
Background:
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an albumin-bound formulation of paclitaxel. This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with advanced non-small cell lung cancer (NSCLC).
Method:
In this multicentre, single arm phase II trial, we enrolled patients with advanced NSCLC who had previously treated more than one chemotherapy regimen. Patients received nab-paclitaxel 80 mg/m[2] days 1, 8, and 15 (21-day cycle). The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints included overall survival (OS), progression-free survival (PFS), the disease control rate (DCR), and safety. The planned enrollment was 30 patients by Simon 2-stage minimax design.
Result:
We enrolled 30 patients. We analyzed endpoints about initially enrolled 24 cases that were available for the evaluation now. Sixty-three % of patients had previous treatment more than 2 regimens. The ORR and DCR were 25% (95% CI 8-42%) and 75%, respectively. Median PFS and OS were 5.8 months and 9.8 months, respectively. No new safety signals were reported; the most common grade ≥3 adverse events included neutropenia (54%), leukopenia (9%), and infection (13%).
Conclusion:
In patients with heavily advanced NSCLC, nab-paclitaxel demonstrated promising antitumor activity; further assessment of nab-paclitaxel monotherapy in this population of patients is supported.
