Abstract 306P
Background
ALK gene rearrangement occurs in 3-7% of non-Sq-NSCLC. Tumor ALK testing by immunohistochemistry (IHC) is recommended. Next generation sequencing (NGS) and fluorescent-in-situ hybridization are validated for samples with inconclusive IHC staining. NGS testing of plasma ctDNA is non-invasive, allowing diagnosis where tissue is inaccessible, and detection of resistance mutations post-progression. One study has reported clinical utility of ALK testing using NGS on plasma, but data are otherwise limited to small samples. We assessed clinical utility of ctDNA NGS for ALK testing for non-Sq-NSCLC in Asia.
Methods
Between September 2015 to May 2020, 464 plasma specimens from 413 patients were analyzed. ctDNA was genotyped using Guardant360 (Guardant Health, Redwood City CA USA). Data on clinicopathologic features and treatment status were extracted from database (Sanomics Ltd, Hong Kong).
Results
ALK fusion and/or resistance mutations were detected in ctDNA of 24 (6%) non-Sq-NSCLC patients. 12 patients (50%) were male. 19 (79%) were adenocarcinoma, 5 (21%) were unknown. Tumor ALK status was available in 21 patients: 13 were ALK positive, 8 previously tested negative. ALK fusion partners included EML4 (85.7%), STRN (9.5%), and KIF5B (4.8%). ALK resistance mutations were detected only in patients with prior ALK inhibitor treatment (8/12, 67%). 13 types of resistance mutations were identified: G1202R, then L1196M, were the most frequent. (Table) Table: 306P
Patient no. | 1a | 1b | 2a | 2b | 3a | 3b | 3c | 4a | 4b | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | |
Prior TKI treatment | NA | Y | NA | NA | Y | Y | Y | O | O | NA | O | Y | Y | Y | N | Y | N | Y | Y | Y | O | Y | NA | Y | O | Y | NA | O | O | |
ALK TKI | Crizotinib | Y | Y | Y | Y | Y | NA | |||||||||||||||||||||||
Ceritinib | Y | Y | Y | |||||||||||||||||||||||||||
Alectinib | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | ||||||||||||||||||||
Lorlatinib | Y | Y | Y | |||||||||||||||||||||||||||
ALK fusion | EML4-ALK | P | P | P | P | P | P | P | P | P | P | P | P | P | P | P | P | P | P | P | ||||||||||
KIF5B-ALK | P | |||||||||||||||||||||||||||||
STRN-ALK | P | P | ||||||||||||||||||||||||||||
ALK resistance mutation | E1210K | P | ||||||||||||||||||||||||||||
D1203N | P | |||||||||||||||||||||||||||||
F1174C | P | |||||||||||||||||||||||||||||
F1174L | P | P | P | |||||||||||||||||||||||||||
G1202R | P | P | P | P | P | |||||||||||||||||||||||||
G1269A | P | |||||||||||||||||||||||||||||
I1171N | P | |||||||||||||||||||||||||||||
I1171T | P | P | ||||||||||||||||||||||||||||
L1152R | P | |||||||||||||||||||||||||||||
L1196M | P | P | P | P | ||||||||||||||||||||||||||
L1196Q | P | |||||||||||||||||||||||||||||
L1198F | P | P | ||||||||||||||||||||||||||||
V1180L | P | P |
NOTE: TKI - tyrosine kinase inhibitor; a, b, c - 1st, 2nd, 3rd ctDNA NGS test; NA - not available; Y - yes; N - no; O - other therapy; P - positive.
Conclusions
NGS testing for ALK fusions and genomic alterations in plasma ctDNA has clinical utility in non-Sq-NSCLC patients in guiding ALK targeted treatment at initial diagnosis and upon cancer progression. Detection rate and distribution of ALK fusion partners are comparable to existing data of tumor ALK testing. Further data on ALK treatment outcomes of patients with detectable ALK fusion on plasma ctDNA is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sanomics Limited.
Funding
Has not received any funding.
Disclosure
K.W.C. Lee, S.T. Wu, P.Y. Lo, C.T. Choy, T.C. Kwong, Y.T.N. Lau. L. Lin, S.W. Lau: Full/Part-time employment: Sanomics Limited.
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