Exploratory biomarker analysis to predict the efficacy of immune checkpoint inhibitors using cell-free DNA

• Project/Area Number: 16K19464
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: Akamatsu Hiroaki 和歌山県立医科大学, 医学部, 講師 (10646582)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肺癌 / リキッドバイオプシー / immunotherapy / lung cancer / Liquid biopsy / 血中循環腫瘍細胞 / cell free DNA / 臨床呼吸器学

Outline of Final Research Achievements

Blood samples were collected from 76 patients who receive immune-checkpoint inhibitors. We did comprehensive somatic mutation analysis using extracted cell-free DNA by next generation sequencing. Addition to that, circulating tumor cells (CTCs) were analyzed for PD-L1 expression by immunohistochemical staining (22c3 antibody). First analysis was done in the first 29 patients. CTCs were detected in all patients, and median number of CTCs were 15 / 5mL (range 1 to 90 / 5mL). Regarding PD-L1 expression, no correlation was observed between CTCs and tumor tissue. Significantly higher disease control rate was observed when >50% of CTCs were positive for PD-L1.
These outcomes described above were reported in American Society of Clinical Oncology 2017, and we are preparing manuscript.

Research Products

• [Journal Article] Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab. (2017)
  • Author(s): Sato K
  • Journal Title: Lung Cancer Volume: 115 Pages: 71-74
  • DOI: 10.1016/j.lungcan.2017.11.019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nivolumab induced radiation recall pneumonitis after two years of radiotherapy. (2017)
  • Author(s): Shibaki R, Akamatsu H, Koh Y, et al.
  • Journal Title: Annals of Oncology Volume: epub Issue: 6 Pages: 1404-1405
  • DOI: 10.1093/annonc/mdx115
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Alectinib for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status (Lung Oncology Group in Kyushu 1401). (2017)
  • Author(s): Iwama E, Goto Y, Akamatsu H, et al.
  • Journal Title: Journal of Thoracic Oncology Volume: 17 Issue: 7 Pages: 30123-5
  • DOI: 10.1016/j.jtho.2017.02.012
  • Peer Reviewed
• [Journal Article] Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. (2017)
  • Author(s): Mok TS, Wu Y-L, Akamatsu H, et al.
  • Journal Title: New England Journal of Medicine Volume: 7 Issue: 7 Pages: 629-640
  • DOI: 10.1056/nejmoa1612674
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Applicability of the Japanese equation for estimating glomerular filtration rate in patients with advanced-stage thoracic cancer. (2016)
  • Author(s): Kikuchi T, Akamatsu H, Mori K, Tanaka A, Kanai K, Hayata A, Tokudome N, Akamatsu K, Koh Y, Nakanishi M, Ueda H, Yamamoto N
  • Journal Title: Respiratory Investigation Volume: 54 Issue: 6 Pages: 479-483
  • DOI: 10.1016/j.resinv.2016.05.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detection of the T790M mutation of EGFR in plasma of advanced non-small cell lung cancer patients with acquired resistance to tyrosine kinase inhibitors (West Japan oncology group 8014LTR study) (2016)
  • Author(s): Takahama T, Sakai K, Takeda M, Azuma K, Hida T, Hirabayashi M, Oguri T, Tanaka H, Ebi N, Sawa T, Bessho A, Tachihara M, Akamatsu H, Bandoh S, Himeji D, Ohira T, Shimokawa M, Nakanishi Y, Nakagawa K, Nishio K.
  • Journal Title: Oncotarget Volume: 7 Issue: 36 Pages: 58492-58499
  • DOI: 10.18632/oncotarget.11303
  • Peer Reviewed / Open Access
• [Presentation] Predictive impact of PD-L1-expressing circulating tumor cells in NSCLC patients treated with nivolumab. (2017)
  • Author(s): Shibaki R, Akamatsu H, Koh Y, Yamamoto N, et al.
  • Organizer: 2017 American Society of Clinical Oncology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2017-06-03
  • Int'l Joint Research
• [Presentation] Sequential tracking of PD-L1 expression on circulating tumor cells in NSCLC patients treated with nivolumab. (2017)
  • Author(s): Akamatsu H, Koh Y, Yamamoto N, et al.
  • Organizer: EORTC-NCI-AACR meeting 2017
  • Int'l Joint Research
• [Presentation] Correlation Between Immune-Related Adverse Events and Efficacy in Non-Small Cell Lung Cancer Treated with Nivolumab. (2017)
  • Author(s): Sato K, Akamatsu H, Murakami E, et al.
  • Organizer: World Conference on Lung Cancer 2017
  • Int'l Joint Research