462P - ROS1 fusion Chinese lung adenocarcinoma patients treated with crizotinib detected using next-generation genotyping from ctDNA

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Xiaomin Niu
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors X. Niu1, Z. Chen1, S. Chuai2, Z. Zhou1, S. Lu1
  • 1Department Of Shanghai Lung Cancer Center, Shanghai Chest Hospital, 200030 - Shanghai/CN
  • 2Burning Rock Diagnostics, Burning Rock Diagnostics, 201114 - Shanghai/CN

Abstract

Background

Chromosomal rearrangements involving the c-ros oncogene 1 (ROS1) have been described as a subset of non-small cell lung cancer (NSCLC). Recently Crizotinib has exhibited marked therapeutic efficacy in the treatment of the ROS1 fusion NSCLC. However, resistance often occurs and repeated biopsy is necessary for tumor genotyping and underlying resistant mechanism. Circulating tumor DNA (ctDNA) represents a promising way to assess tumor genetic profile non-invasively. This study aims to assess whether liquid biopsies accurately screen disease diagnosis and reflect the response to Crizotinib treatment through analysis of ctDNA for ROS1 fusions in patients with lung adenocarcinoma, and to elucidate the underlying mechanisms of ROS1 targeted drug resistance.

Methods

Eight plasma samples were collected from a cohort of 6 patients with ROS1 fusion advanced stage lung adenocarcinoma, confirmed by fluorescent in situ hybridization (FISH) in tissue. One out of all six patients treated with Crizotinib had three different time points, which are the points at baseline, partial response and disease progression, irrespectively; while the other five patients only had the baseline samples. A prospective-retrospective analysis on ctDNA was further performed from archived plasma samples using our ctDNA panel with concurrent CT or MRI imaging at the baseline and 8-week intervals during responsive Crizotinib treatment, and at progressive disease.

Results

Four out of six patients showed detectable levels of ROS1 fusion in ctDNA at baseline. Upon treatment with Crizotinib, response rate is inversely correlated with levels of ROS1 fusion. One patient with progressive disease, patient 1, exhibited a detectable CD74-ROS1 fusion with 13.5% concentration at baseline; it was undetectable at partial response and re-elevated to 8.2% accompanied by an acquired G2032R mutation when disease progressed.

Conclusions

Our ctDNA panel could be applied clinically to detect ROS1 fusion from plasma for accurate screening where detection correlates with disease status, and could distinguish mutations associated with Crizotinib induced resistance in patients with NSCLC, thus facilitating personalized cancer therapy.

Clinical trial indentification

Legal entity responsible for the study

Shun Lu

Funding

Shanghai Chest Hospital

Disclosure

All authors have declared no conflicts of interest.