Very early response of circulating tumour–derived DNA in plasma predicts efficacy of nivolumab treatment in patients with non–small cell lung cancer. (November 2017)

• Record Type: Journal Article
• Authors: Iijima, Yuki; Hirotsu, Yosuke; Amemiya, Kenji; Ooka, Yoshihiko; Mochizuki, Hitoshi; Oyama, Toshio; Nakagomi, Takahiro; Uchida, Yoshinori; Kobayashi, Yoichi; Tsutsui, Toshiharu; Kakizaki, Yumiko; Goto, Taichiro; Miyashita, Yoshihiro; Omata, Masao
• Is Part Of: European journal of cancer. Volume 86(2017)
• Page Start: 349
• Page End: 357
• Publication Date: 2017-11
• Subjects: Circulating tumour DNA -- Immunotherapy -- Nivolumab -- Lung cancer -- PD-1; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.09.004
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: First study to predict efficacy of immunotherapy by weekly changes of ctDNA after the treatment. Only the analysis of plasma DNA lack specificity as ctDNA. Analysis of plasma DNA was taken proof as ctDNA by the analysis of tumor tissue. Efficacy of immunotherapy can be predicted within early periods by the use of circulating tumour DNA.