A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs.
Lung Cancer
; 134: 46-51, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31319994
ABSTRACT
OBJECTIVES:
We evaluated the safety and efficacy of the combination therapy of afatinib, an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and ruxolitinib, a JAK1/2 selective inhibitor, in patients with EGFR mutant NSCLC progressing on at least one kind of EGFR-TKI. MATERIALS ANDMETHODS:
In this phase Ib open-label study, we used a 3â¯+â¯3 dose-escalation design. Patients with histologically diagnosed EGFR-mutant stage IV NSCLC and documented disease progression on EGFR-TKI therapies were enrolled. Afatinib only was administered on day 1 through day 8 (run-in period), then ruxolitinib was administered concurrently with afatinib until disease progression. The primary endpoints were to determine the dose-limiting toxicity (DLT) and a recommended phase II dose of the combination regimen. We also included a dose confirmation cohort for the highest dose, and an expansion cohort for T790â¯M mutation.RESULTS:
As of October 2017, 30 patients participated in the study, of which 20 had T790â¯M mutations. Because no DLT was observed in nine patients at the highest dose level (50â¯mg afatinib once daily plus 25â¯mg ruxolitinib twice daily), nine patients with T790â¯M mutations were enrolled in a dose-expansion cohort. Frequent adverse events included diarrhea (G3 in 3 of 22 cases), anemia (G3 in 1 of 26 cases), paronychia (G1/2 in 14 cases), acneiform rash (G1 in 13 cases), and oral mucositis (G1/2 in 12 cases). Objective response rate was 23.3% (no complete response [CR] and 7 partial responses [PR]) and disease control rate was 93.3% (no CR, 7 PR and 21 stable diseases). The median progression-free survival was 4.9 months (95% CI, 2.4-7.5).CONCLUSION:
The combination of afatinib and ruxolitinib was tolerated by patients, with modest clinical activity observed in NSCLC with acquired resistance to EGFR-TKIs (NCT02145637).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
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Mutação
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article