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A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib.
J Thorac Oncol 2017; 12(5):804-813JT

Abstract

INTRODUCTION

The availability of high-quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK)-positive NSCLC who can potentially benefit from treatment with crizotinib. Here we present data on the recently approved Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ), the only immunohistochemistry (IHC)-based assay linked to treatment outcome.

METHODS

NSCLC specimens prospectively tested for anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by flourescent in situ hybridization (FISH) in the PROFILE 1014 clinical trial of crizotinib versus chemotherapy (N = 1018, including 179 ALK-positive and 754 ALK-negative specimens) were evaluated using the ALK (D5F3) CDx assay. Hazard ratios for progression-free survival comparing crizotinib and chemotherapy for ALK IHC-positive patients and ALK FISH-positive patients, as well as for concordance with the enrollment ALK FISH assay, were determined.

RESULTS

Results from both assays were obtained for 933 cases. Percent positive, negative, and overall agreement rates were 86.0% , 96.3%, and 94.3%, respectively. There were 53 discrepant cases, of which 25 were ALK FISH-positive/ALK IHC-negative and 28 were ALK FISH-negative/ALK IHC-positive. The hazard ratios using observed outcomes were 0.401 for ALK FISH-positive/ALK IHC-positive cases and 0.407 for all ALK FISH-positive cases tested with ALK IHC versus 0.454 for all ALK FISH-positive cases enrolled in the trial. Outcome data for ALK FISH-negative/ALK IHC-positive cases were not available for analysis. Between-reader agreement rates for ALK IHC involving three independent laboratories exceeded 98%.

CONCLUSIONS

The ALK (D5F3) CDx assay is a stand-alone companion diagnostic test for identification of patients for treatment with crizotinib. This automated assay provides an effective option to accurately and rapidly identify patients with ALK-positive NSCLC. The simple binary scoring algorithm results in high reader-to-reader precision.

Authors+Show Affiliations

Ventana Medical Systems, Tucson, Arizona. Electronic address: trish.thorne-nuzzo@roche.com.Ventana Medical Systems, Tucson, Arizona.Ventana Medical Systems, Tucson, Arizona.Ventana Medical Systems, Tucson, Arizona.Ventana Medical Systems, Tucson, Arizona.Laboratory Corporation of America Holdings, Shelton, Connecticut.Laboratory Corporation of America Holdings, Shelton, Connecticut.Caris Life Sciences, Phoenix, Arizona.Pfizer Oncology, La Jolla, California.Ventana Medical Systems, Tucson, Arizona.Personal Genome Diagnostics, Baltimore, Maryland.Ventana Medical Systems, Tucson, Arizona.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28147239

Citation

Thorne-Nuzzo, Trish, et al. "A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment With Crizotinib." Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, vol. 12, no. 5, 2017, pp. 804-813.
Thorne-Nuzzo T, Williams C, Catallini A, et al. A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib. J Thorac Oncol. 2017;12(5):804-813.
Thorne-Nuzzo, T., Williams, C., Catallini, A., Clements, J., Singh, S., Amberson, J., ... Towne, P. (2017). A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, 12(5), pp. 804-813. doi:10.1016/j.jtho.2017.01.020.
Thorne-Nuzzo T, et al. A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment With Crizotinib. J Thorac Oncol. 2017;12(5):804-813. PubMed PMID: 28147239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib. AU - Thorne-Nuzzo,Trish, AU - Williams,Crystal, AU - Catallini,Alice, AU - Clements,June, AU - Singh,Shalini, AU - Amberson,James, AU - Dickinson,Kim, AU - Gatalica,Zoran, AU - Ho,Steffan N, AU - Loftin,Isabell, AU - McElhinny,Abigail, AU - Towne,Penny, Y1 - 2017/01/29/ PY - 2016/10/28/received PY - 2016/12/19/revised PY - 2017/01/06/accepted PY - 2017/2/2/pubmed PY - 2018/1/5/medline PY - 2017/2/2/entrez KW - ALK IHC KW - Anaplastic lymphoma kinase KW - Companion diagnostic assay KW - NSCLC KW - Targeted therapy SP - 804 EP - 813 JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JO - J Thorac Oncol VL - 12 IS - 5 N2 - INTRODUCTION: The availability of high-quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK)-positive NSCLC who can potentially benefit from treatment with crizotinib. Here we present data on the recently approved Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ), the only immunohistochemistry (IHC)-based assay linked to treatment outcome. METHODS: NSCLC specimens prospectively tested for anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by flourescent in situ hybridization (FISH) in the PROFILE 1014 clinical trial of crizotinib versus chemotherapy (N = 1018, including 179 ALK-positive and 754 ALK-negative specimens) were evaluated using the ALK (D5F3) CDx assay. Hazard ratios for progression-free survival comparing crizotinib and chemotherapy for ALK IHC-positive patients and ALK FISH-positive patients, as well as for concordance with the enrollment ALK FISH assay, were determined. RESULTS: Results from both assays were obtained for 933 cases. Percent positive, negative, and overall agreement rates were 86.0% , 96.3%, and 94.3%, respectively. There were 53 discrepant cases, of which 25 were ALK FISH-positive/ALK IHC-negative and 28 were ALK FISH-negative/ALK IHC-positive. The hazard ratios using observed outcomes were 0.401 for ALK FISH-positive/ALK IHC-positive cases and 0.407 for all ALK FISH-positive cases tested with ALK IHC versus 0.454 for all ALK FISH-positive cases enrolled in the trial. Outcome data for ALK FISH-negative/ALK IHC-positive cases were not available for analysis. Between-reader agreement rates for ALK IHC involving three independent laboratories exceeded 98%. CONCLUSIONS: The ALK (D5F3) CDx assay is a stand-alone companion diagnostic test for identification of patients for treatment with crizotinib. This automated assay provides an effective option to accurately and rapidly identify patients with ALK-positive NSCLC. The simple binary scoring algorithm results in high reader-to-reader precision. SN - 1556-1380 UR - https://www.unboundmedicine.com/medline/citation/28147239/A_Sensitive_ALK_Immunohistochemistry_Companion_Diagnostic_Test_Identifies_Patients_Eligible_for_Treatment_with_Crizotinib_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1556-0864(17)30044-8 DB - PRIME DP - Unbound Medicine ER -