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Z. Chen
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-056 - Tumor Heterogeneity in Lesion Specific Response Creates ROS1 Fusion Mediating Resistance to Gefitinib in EGFR 19 Deletion Lung Adenocarcinoma (ID 6207)
14:30 - 14:30 | Author(s): Z. Chen
- Abstract
Background:
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer related death worldwide. In recent years molecular characterisation of NSCLC has led to the identification of several driver events including EGFR constitutive activation, ALK-rearrangement and ROS1 fusion. Whilst there are several mechanisms of EGFR-mutation stated in the literature, how genomic heterogeneity related with acquired EGFR resistance to second targeted agent affects response to subsequent therapy has not been noted.
Methods:
We studied EGFR-TKI, gefitinib, in an EGFR 19 deleted lung adenocarcinoma patient to assess whether tissue and liquid biopsy could be integrated with radiologic imagings to demonstrate the impact of individual actionable driver mutation on lesion specific response.
Results:
A 60-year old female, with no previous or family history of malignancy initially presented with EGFR 19 deletion mutation, ROS1 fusion negative and ALK rearrangement negative stage IV, T2aN3M1a lung adenocarcinoma detected in primary lung cancer tissue at the first diagnosis. Biopsy of this patient’s metastatic right cervical lymph node following prolonged response to gefitinb led to the loss of detection of EGFR mutation, and the novel mechanism of acquired resistance with EZR-ROS1 fusion where crizotinib was demonstrated to have good efficacy in all lesions, especially the enlarged lymphadenopathy, and also including diminishing efficacy on metastatic brain lesions. In circulating tumor DNA (ctDNA), mutant EGFR levels disappeared followed by gefitinib treatment, and a recognized EZR-ROS1 fusion was meanwhile identified before crizotinib therapy.
Conclusion:
This case displays tumor heterogeneity in action, where targeted therapy selects against primary drivers, allowing for the establishment of sub-colonies with new drivers within the specific lesion. Parallel analysis of tumor biopsies when disease progressed and ctDNA monitoring showed that lesion specific radiographic responses to subsequent targeted therapies could be driven by district resistant mechanism in the separate tumor lesions within the same patient. This demonstrates that the importance of molecular heterogeneity surveillance ensuing from acquired resistance in managing NSCLC, and the usage of liquid biopsies to allow for a holistic viewpoint of the molecular landscape of this heterogeneous disease.
