Resistance mechanis of molecular targeted therapy and tumor micro environment as the immune-checkpoint inhibitor's biomarker
| Project/Area Number |
16K21506
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor diagnostics
Medical genome science
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | バイオマーカー / 個別化医療 / 免疫チェックポイント阻害薬 / 免疫チェックポイント / 免疫チェックポイント阻害剤 / 分子標的治療薬 |
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| Outline of Final Research Achievements |
The efficacy of PD-1 blockade in EGFR mutated NSCLC with different mechanisms of acquired resistance to EGFR-TKIs is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR.We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations.
Efficacy of nivolumab tended to increase as the PD-L1 expression level increased with cutoff values of 10% and 50%.The proportion of tumors with a PD-L1 level of10% or50% was higher among T790M-negative patients than among -positive patients. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden.
T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level.
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Report
(3 results)
Research Products
(3 results)
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[Journal Article] Tumor Immune Microenvironment and Nivolumab Efficacy in EGFR Mutation-Positive Non-Small Cell Lung Cancer Based on T790M Status After Disease Progression During EGFR-TKI Treatment2017
Author(s)
K. Haratani, H. Hayashi*, T. Tanaka, H. Kaneda, Y. Togashi, K. Sakai, K. Hayashi, S. Tomida, Y. Chiba, K. Yonesaka, Y. Nonagase, T. Takahama, J. Tanizaki, K. Tanaka, T. Yoshida, K. Tanimura, M. Takeda, H. Yoshioka, T. Ishida, T. Mitsudomi, K. Nishio and K. Nakagawa
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Journal Title
Annals of Oncology
Volume: in press
Issue: 7
Pages: 1532-1539
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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