Variability in lung cancer response to ALK inhibitors cannot be explained by the diversity of ALK fusion variants.
Biochimie
; 154: 19-24, 2018 Nov.
Article
em En
| MEDLINE
| ID: mdl-30071258
ABSTRACT
Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKIs). These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation. We retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (nâ¯=â¯23), ceritinib (nâ¯=â¯39) or alectinib (nâ¯=â¯2). ALK fusion variants were genotyped by PCR. Median progression-free survival (PFS) approached to 18 and 21 months in subjects with "short" (v.3a/b, v.5a/b) vs. "long" (TAPE-domain containing) fusion variants (pâ¯=â¯0.783), respectively; similar data were obtained while comparing EML4/ALK variant 1 vs. other ALK translocations (19 and 21 months, respectively; pâ¯=â¯0.604). Objective response rates were also strikingly similar in the above groups ("short" 88%, "long" 77%, pâ¯=â¯0.479; variant 1 76%, other translocations 81%, pâ¯=â¯0.753). Furthermore, ALK variants did not influence the disease outcomes when patients treated by crizotinib and ceritinib were analyzed separately. Overall, PFS on ALK TKI did not depend on whether the drug was administered upfront or after chemotherapy. Ceritinib produced significantly longer PFS than crizotinib (pâ¯=â¯0.022). In conclusion, this study revealed that distinct ALK translocation variants render similar clinical responsiveness to ALK inhibitors.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fusão Oncogênica
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Receptores Proteína Tirosina Quinases
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Carcinoma Pulmonar de Células não Pequenas
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Inibidores de Proteínas Quinases
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Neoplasias Pulmonares
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article