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A. Kumanogoh
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-047 - Carboplatin/ Weekly Nab-PTX in Elderly Patients with Previously Untreated Advanced Squamous NSCLC Selected Based on MNA-SF (ID 7582)
09:30 - 09:30 | Author(s): A. Kumanogoh
- Abstract
Background:
This multicenter, single-arm, open-label, phase 2 study assessed the efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer, selected based on the Mini Nutritional Assessment short-form scores (MNA-SF).
Method:
Patients received carboplatin (area under the curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m[2]) on Days 1, 8, and 15, every 28 days for ≤4 cycles. Eligibility criteria included an MNA-SF score of ≥8 points. The primary endpoint was the objective response rate.
Result:
Thirty patients with a median age of 76 (range, 70–83) years were enrolled. The objective response rate was 50.0% (95% confidence interval: 31.3–68.7%), which met the primary objective of this study. The disease control rate was 73.3% (95% confidence interval: 54.1–87.7%). At a median follow-up of 15.0 months, the median progression-free and overall survival was 7.1 and 19.1 months, respectively. The most common treatment-related adverse event of Grade ≥3 was neutropenia (66.7%). Non-hematological adverse events of Grade ≥3 were minor. Well-nourished patients, based on the MNA-SF, experienced fewer adverse events of Grade ≥3 compared to patients at risk of malnutrition. All treatment-related adverse events were tolerable and reversible. There were no treatment-related deaths.
Conclusion:
Carboplatin plus weekly nanoparticle albumin-bound paclitaxel is effective and well tolerated as a first-line treatment for elderly patients with advanced squamous non-small-cell lung cancer. Eligibility based on MNA-SF screening may be useful in determining acceptable toxicity.
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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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P2.07-009 - Monitoring Nivolumab Binding as a Method to Clarify the Residual Therapeutic Effects in Previously Treated Lung Cancer Patients (ID 8098)
09:30 - 09:30 | Author(s): A. Kumanogoh
- Abstract
Background:
Although the biological durability of Nivolumab, the PD-1 blocking antibody, was reported to continue longer than 12 weeks, the maximum duration of its efficacy, along with toxicity, after discontinuation and the correlation between residual binding and clinical events in cases of sequential therapeutic regimens remain unclear.
Method:
Peripheral blood, pleural effusion and bronchoalveolar lavage fluid were obtained from non-small cell lung cancer patients previously treated with Nivolumab. To evaluate the efficacy of the treatment, we developed a simple technique to identify Nivolumab binding status — complete binding, partial binding and no binding — in T cells from patient samples using flowcytometry, which can also be used to obtain T cell differentiation markers and transcriptome profiles, particularly in the Nivolumab bound T cell population. Based on this method, we tracked the binding status in T cells primarily from peripheral blood in patients who received a sequential therapeutic regimen after Nivolumab treatment.
Result:
While the decrease in frequency of Nivolumab binding after discontinuation was observed in all cases where long term monitoring was possible, Nivolumab binding in T cells from peripheral blood was detected until more than 20 weeks, though effective binding could have ceased before that time point. We found that the direct effects on Nivolumab binding via sequential treatment were limited. Finally, we observed in clinical cases that our monitoring technique was also helpful in understanding the cause of clinical events and its residual efficacy in patients who previously received Nivolumab.
Conclusion:
Monitoring of Nivolumab binding to T cells after discontinuation can be valuable when planning sequential therapeutic regimens in the following ways: estimating the potential residual efficacy, predicting the risk of immune-related adverse events and the time of relapse due to complete loss of efficacy, and investigating the changes in the immune profile in Nivolumab bound T cells.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-023 - Semaphorin 7A Reduces Response to EGFR-TKI Treatment via Apoptosis in Human Lung Adenocarcinoma (ID 8074)
09:30 - 09:30 | Author(s): A. Kumanogoh
- Abstract
Background:
Most patients harboring epidermal growth factor receptor (EGFR) mutations experience relapse to EGFR-Tyrosin kinase inhibitors (TKI). So it is necessary to overcome the resistance to EGFR-TKI. We found that Semaphorin 7A (SEMA7A) is upregulated by EGFR signals. The role of SEMA7A in human lung adenocarcinoma is unknown, so we annlyzed the function of SEMA7A in human lung adenocarinoma.
Method:
We compared transcriptomes of NIH3T3 cell lines overexpressing wild type (WT) EGFR with Next, we investigated which pathways regulated the expression of SEMA7A in human lung adenocarcinoma cell line. Furthermore, we investigated the expression of SEMA7A by immunohistochemistry (IHC), and the correlation of SEMA7A and phosphorylation S6 (pS6) in 129 lung adenocarcinoma patients were analyzed. We also investigated the correlation of SEMA7A expression with the prognosis or drug response in 44 stage IV lung adenocarcinoma patients. Finally, we investigated the efficacy of EGFR-TKI in SEMA7A WT and KO (by CRISPR/CAS9) in vitro and in vivo.
Result:
The expression of SEMA7A was regulated by EGFR signals. Furthermore, the expression of SEMA7A was downregulated by mTOR signals in human lung adenocarinoma cells and clinical samples. High SEMA7A lung cancers tended to get EGFR-TKI resistance, in vivo, in vitro via apoptosis. In clinical samples, high SEMA7A expression tumor tended to get EGFR-TKI resistance.
Conclusion:
We revealed that the SEMA7A regulated the efficacy to EGFR-TKI via apoptosis.
