ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib.
Lung Cancer
; 138: 13-18, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31630043
ABSTRACT
OBJECTIVE:
Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHCâ¯+â¯FISH-. The aim of this study was to collect ALK IHCâ¯+â¯cases and compare within this group response to crizotinib treatment of ALK FISHâ¯+â¯cases with ALK FISH- cases. MATERIALS ANDMETHODS:
In this European prospective multicenter research study patients with Stage IV ALK IHCâ¯+â¯NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH.RESULTS:
Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (nâ¯=â¯94) ALK IHCâ¯+â¯cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC+/FISH+) and 16 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1â¯year for ALK concordant and discordant was 58% and 20%, respectively (HRâ¯=â¯2.4; 95% CI 0.78-7.3; pâ¯=â¯0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010.CONCLUSION:
ALK IHCâ¯+â¯FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Crizotinib
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Quinasa de Linfoma Anaplásico
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Neoplasias Pulmonares
Tipo de estudio:
Clinical_trials
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Guideline
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lung Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article