Virtual Library
Start Your Search
Yu Yang
Author of
-
+
P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.01-108 - Temporal Heterogeneity of Resistant Mutations in Sequential ALK TKI Treated Lung Cancer Revealed by NGS-Based Liquid Biopsy (ID 13488)
16:45 - 18:00 | Presenting Author(s): Yu Yang
- Abstract
Background
Crizotinib and several next-generation ALK TKIs have been widely applied in the treatment of ALK-positive lung cancer patients. However, drug resistance is eventually developed to these ALK TKIs via heterogeneous resistance mechanisms, which is needed to be further explored. Due to the invasiveness and feasibility of repetitive tissue biopsies, liquid biopsy has become a promising alternative for dynamically monitoring tumor genomic evolution and guides decision-making for treatment adjustment.
a9ded1e5ce5d75814730bb4caaf49419 Method
Primary tumor sample of a 71-year-old male patient diagnosed with stage IV lung adenocarcinoma was subjected for targeted next-generation sequencing (NGS) for identification of driver mutations. Mutation profiles of circulating tumor DNA (ctDNA) from seven sequential plasma samples during the treatment course of crizotinib, brigatinib, and lorlatinib were closely monitored.
4c3880bb027f159e801041b1021e88e8 Result
The dynamic mutation profiles during the disease course were represented in the Figure. As EML4-ALK v1 fusion was detected in the primary tumor, the patient was administrated with crizotinib and reached a progression-free survival (PFS) of 11 months when ALK G1269A was identified upon progression. As a result, brigatinib, a second generation ALK TKI overcoming G1269A-driven resistance, was applied. Dynamic monitoring of patient’s ctDNA during brigatinib treatment showed a dramatic drop of G1269A mutant allele frequency (MAF) to undetectable level, whereas a novel F1174L became the dominant clone. The disease progressed after 9-month of brigatinib treatment, and the patient was switched to lorlatinib. A third mutation E1210K quickly overtook F1174L as the dominant clone with the accumulation of more concomitant mutations towards the end of the treatment (8 different mutations) with a PFS of 9 months. Interestingly, brigatinib-sensitive G1269A came back after 6-month of lorlatinib treatment.
8eea62084ca7e541d918e823422bd82e Conclusion
Temporal heterogeneity of ALK activating mutations was observed along the treatment course of different TIKs via NGS-based liquid biopsy, which could provide guidance for stepwise treatment strategy for better patient care.
6f8b794f3246b0c1e1780bb4d4d5dc53