In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 9063-9063
Abstract:
9063 Background: Crizotinib is a standard of care in anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancers (NSCLC). Undoubtedly,the resistance to crizotinib is a current bottleneck which resists its clinical application. However, there are few reports about the primary resistance to crizotinib, especially the difference between the primary and acquired resistance. Methods: Totally,171 ALK-positive NSCLC patients treated with crizotinib were reviewed at the Guangdong General Hospital in China from October 2010 to July 2016. The status of an ALK gene rearrangement was assessed by Vysis ALK Break Apart fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), or ALK Ventana immunohistochemistry (IHC). Among 18 patients with primary resistance, 12 had tumor tissue (n = 6) or plasma (n = 6) at the baseline and meanwhile tumor tissue (n = 2) or plasma (n = 2) specimens were collected for 4 patients after primary resistance. Next generation sequencing was used to test the tissue or plasma from 16 patients with primary resistance to crizotinib. Results: Among 171 patients treated with crizotinib, 47.9% (82/171) developed acquired resistance, and 10.5%(18/171) had primary resistance. Using the specimens at the baseline, there were 6 ( 33.0%) patients with uncommon ALK fusion partners, 4 (22.2 %) with BIM deletion polymorphism, 2 (11.1%) with PTEN/mTOR mutations, and 1 (5.5 %) with a pre-existing ALK G3709A mutation.These uncommon ALK fusion partners included ZC3H8-ALK, ALK-LOC102723854 and ALK-DTNB-ASXL2. In addition, one patient was found to coexsist with KIT mutation after primary resistance. Median PFS was significantly shorter in patients with primary resistance than those with acquired resistance (2.2 vs. 10.8 months, P 〈 0.001). Conclusions: Uncommon ALK fusion partners, BIM deletion polymorphism, PTEN/mTOR mutation, pre-existing ALK G3709A mutation and KIT mutation might contribute to molecular mechanisms of primary resistance to crizotinib in ALK-positive NSCLC. Further investigations are warranted to overcome these primary resistances.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.9063
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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