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MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
MA 05.08 - Very Early Response of Circulating Tumor Derived DNA Predict the Efficacy of Treatment by Nivolumab in Patients with Non-small Cell Lung Cancer (ID 8303)
15:45 - 17:30 | Author(s): Y. Miyashita
Immunotherapy has become one of the options among the treatments of lung cancer. Nivolumab was first proven to have the utility as a second line treatment for non-small cell lung cancer. However, predictive factor of its efficacy is unknown. In recent years, studies have evolved on circulating tumor DNA (ctDNA). Clinical applications expanded and included prediction of prognosis, monitoring treatment effects and acquired resistance of driver genes, and assessment of residual tumor burden of resected cancer. In this study, we took cases in which tumor tissue was surgically resected or obtained by biopsy and the corresponding somatic mutations in plasma were studied. Then, we used these somatic mutations presumably derived from original tumor tissue as “tumor markers”. We took serial blood samples before and after starting nivolumab and examined to see whether early change of the level of ctDNA can predict long term treatment outcomes.
Fourteen patients who were treated by nivolumab from February 1st to September 30th in 2016 were studied. Peripheral blood samples were collected from the patients before, 1, 2, 4, 6 and 8 weeks after the initiation of nivolumab treatment. To identify somatic mutations in tissue and total plasma DNA, we performed targeted sequencing using “lung cancer panel” spanning whole exons of these 53 genes, and next generation sequencing was performed. Gene mutations detected in both tumor tissue and plasma were defined here as circulating tumor DNA (ctDNA). Early response of the level of ctDNA after starting nivolumab was evaluated to see whether it could predict treatment outcome.
Of 14 cases, 6 cases were Responders, and 8 Non-responders. ctDNA was detected more often in the serial plasma samples of patients carrying high tumor burden (p=0.02). In addition, basal and serial ctDNA analysis revealed that decrease of allelic frequency (AF) level within 2 weeks correlated with the good durable response, and on the contrary, the increase with no or poor response.
In patients carrying high tumor burden, plasma analysis of ctDNA which was validated by tumor tissue, revealed the durable good response of nivolumab could be predicted within 2 weeks.