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Poster display session

1699 - ALK fusion variants detection by targeted RNA-next generation sequencing and clinical responses to crizotinib in ALK-positive non-small cell lung cancer

Date

09 Sep 2017

Session

Poster display session

Presenters

Anne Mc Leer

Citation

Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380

Authors

A. Mc Leer1, M. Duruisseaux2, J. Pinsolle2, S. Dubourg1, J. Mondet1, M. Phillips-Houlbracq2, N. Magnat1, J. Fauré3, A. Chatagnon3, F. de Fraipont1, M. Giaj Levra2, A.C. Toffart2, G. Ferretti4, E. Brambilla5, P. Hainaut1, D. Moro-Sibilot2, S. Lantuéjoul5

Author affiliations

  • 1 Cancer Molecular Genetics Platform, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
  • 2 Thoracic Oncology, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
  • 3 Molecular Biology Platform, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
  • 4 Radiology And Imaging Dept, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
  • 5 Pathology Department, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
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Resources

Abstract 1699

Background

The aim of the present study was to assess the yields of an amplicon-based parallel sequencing (RNA-seq) assay for ALK fusion transcript variants detection in comparison with immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) in a selected population of ALK-positive and ALK-negative non-small cell lung cancer (NSCLC) cases, and to evaluate the impact of the ALK variant on crizotinib efficacy.

Methods

Our population comprised fifty-three NSCLC cases positive for ALK by IHC and/or FISH and twenty-three ALK-negative samples. For the ALK-positive samples, a distinction was made between ‘truly’ IHC/FISH positive or ‘truly’ IHC/FISH negative samples, and the samples for which the IHC and/or FISH were equivocal (IHC) or borderline-positive (FISH).

Results

On the overall population, RNA-seq sensitivity and specificity were of 80% and 100%, respectively when IHC and FISH were combined and of 100% for both for ‘truly’ positive samples. Interestingly, this assay also appeared to be a promising rescue technique in equivocal and/or borderline-positive IHC/FISH cases. Moreover, when crizotinib efficacy was evaluated according to the type of ALK variant detected, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants. A lack of efficacy of crizotinib was noted in KLC1-ALK variants.

Conclusions

RNA-seq detects ALK rearrangements with a high sensitivity and specificity and may be particularly useful in equivocal/borderline-positive IHC/FISH cases. In addition, it offers a unique opportunity to identify ALK fusion variants and to evaluate their predictive value for ALK inhibitors efficacy.

Clinical trial identification

Not a clinical trial

Legal entity responsible for the study

Anne Mc Leer

Funding

MD was the recipient of the IFCT (Intergroupe Francophone de Cancérologie Thoracique) Alain Depierre Grant in 2014. JP was the recipient of the ARISTOT (Association de Recherche, d’Information Scientifique et Thérapeutique en Oncologie Thoracique) grant in 2016. This work received funding from the Grenoble-Alpes University Hospital (DRCI REALK project) and from the French Institut National du Cancer (INCa). Intergroupe Francophone de Cancérologie Thoracique, Association de Recherche, d’Information Scientifique et Thérapeutique en Oncologie Thoracique, Grenoble-Alpes University Hospital (DRCI REALK project), French Institut National du Cancer (INCa).

Disclosure

A. Mc Leer: Research funding from Novartis and Pfizer, reimbursed for travel, accommodation by ThermoFisher, ZytoVision/Clinisciences, Astra-Zeneca, Novartis, Pfizer and Roche and has served as a consultant for Pfizer. M. Duruisseaux: Research funding from Novartis and Pfizer. Reimbursed for travel, accommodation, and/or other expenses by Novartis, Pfizer and Roche. A.C. Toffart: Reimbursed for travel, accommodation, and/or other expenses by Novartis, Pfizer and Roche. D. Moro-Sibilot: Research funding from Pfizer. Served as a consultant (advisory board) for Novartis, Pfizer and Roche. S. Lantuejoul: Consultant in advisory boards for BMS, MSD, Pfizer, Novartis, Astra-Zeneca, Roche, Boehringer Ingelheim. All other authors have declared no conflicts of interest.

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