Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.
J Clin Oncol
; 42(22): 2660-2670, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38822758
ABSTRACT
PURPOSE:
Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China.METHODS:
TRUST-I evaluated TKI-naÑve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety.RESULTS:
As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naÑve n = 106; crizotinib pretreated n = 67). In TKI-naÑve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naÑve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness 23%; dysgeusia 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.CONCLUSION:
Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
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Proteínas Proto-Oncogênicas
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Carcinoma Pulmonar de Células não Pequenas
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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
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China