Very early response of circulating tumour–derived DNA in plasma predicts efficacy of nivolumab treatment in patients with non–small cell lung cancer

Yuki Iijima, Yosuke Hirotsu, Kenji Amemiya, Yoshihiko Ooka, Hitoshi Mochizuki, Toshio Oyama, Takahiro Nakagomi, Yoshinori Uchida, Yoichi Kobayashi, Toshiharu Tsutsui, Yumiko Kakizaki, Taichiro Goto, Yoshihiro Miyashita, Masao Omata

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37 Citations (Scopus)

Abstract

Introduction Immunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non–small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown. Methods This study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome. Results Of the 14 patients, six were responders and eight were non-responders. DNA was analysed in both tumour tissue and plasma samples. Only somatic mutations confirmed by analysis of tumour tissue were defined as ctDNA. ctDNA was detected more often in the serial plasma samples of patients with high tumour volume (TV) (p = 0.02). ctDNA was detected in seven cases; basal and serial ctDNA analysis revealed that a decrease in allelic frequency (AF) of ctDNA showed high-level correspondence with a good durable response. When “2 weeks” was set as a clinically significant time point, changes in representative mutations of each case, defined as one of the highest baseline AF, showed 100% concordance with the response. Conclusions In patients with high TV, plasma analysis of ctDNA, as validated by tumour tissue, suggested that a durable good response to nivolumab could be predicted within 2 weeks.

Original languageEnglish
Pages (from-to)349-357
Number of pages9
JournalEuropean Journal of Cancer
Volume86
DOIs
Publication statusPublished - 2017 Nov
Externally publishedYes

Keywords

  • Circulating tumour DNA
  • Immunotherapy
  • Lung cancer
  • Nivolumab
  • PD-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Iijima, Y., Hirotsu, Y., Amemiya, K., Ooka, Y., Mochizuki, H., Oyama, T., Nakagomi, T., Uchida, Y., Kobayashi, Y., Tsutsui, T., Kakizaki, Y., Goto, T., Miyashita, Y., & Omata, M. (2017). Very early response of circulating tumour–derived DNA in plasma predicts efficacy of nivolumab treatment in patients with non–small cell lung cancer. European Journal of Cancer, 86, 349-357. https://doi.org/10.1016/j.ejca.2017.09.004