Very early response of circulating tumour–derived DNA in plasma predicts efficacy of nivolumab treatment in patients with non–small cell lung cancer
| Autor: | Taichiro Goto, Toshio Oyama, Masao Omata, Yoichi Kobayashi, Yoshinori Uchida, Kenji Amemiya, Toshiharu Tsutsui, Hitoshi Mochizuki, Takahiro Nakagomi, Yoshihiro Miyashita, Yoshihiko Ooka, Yuki Iijima, Yumiko Kakizaki, Yosuke Hirotsu |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research Pathology medicine.medical_specialty Lung Neoplasms Time Factors Somatic cell medicine.medical_treatment Concordance Circulating Tumor DNA 03 medical and health sciences chemistry.chemical_compound Basal (phylogenetics) Antineoplastic Agents Immunological 0302 clinical medicine Gene Frequency Predictive Value of Tests Carcinoma Non-Small-Cell Lung Internal medicine Biomarkers Tumor medicine Humans Lung cancer Allele frequency Aged Retrospective Studies business.industry Antibodies Monoclonal Immunotherapy Middle Aged medicine.disease Tumor Burden Nivolumab Treatment Outcome 030104 developmental biology chemistry 030220 oncology & carcinogenesis Mutation Female business DNA |
| Zdroj: | European Journal of Cancer. 86:349-357 |
| ISSN: | 0959-8049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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