Indirect treatment comparison of larotrectinib versus entrectinib in treating patients with TRK gene fusion cancers

Information regarding the comparative efficacy of first‐generation receptor tyrosine kinase inhibitors is limited. This matching‐adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (...

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Detalles Bibliográficos
Autores: García-Foncillas López, Jesús Miguel, Bokemeyer, Carsten, Italiano, Antoine, Keating, Karen, Paracha, Noman, Fellous, Marc, Marian, Marisca, Fillbrunn, Mirko, Gao, Wei, Ayyagari, Rajeev, Lassen, Ulrik
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/707596
Acceso en línea:http://hdl.handle.net/10486/707596
https://dx.doi.org/10.3390/cancers14071793
Access Level:acceso abierto
Palabra clave:clinical efficacy
entrectinib
larotrectinib
NTRK gene fusion
safety
Medicina
Descripción
Sumario:Information regarding the comparative efficacy of first‐generation receptor tyrosine kinase inhibitors is limited. This matching‐adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO‐TRK‐14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA‐372‐001 (EudraCT 2012‐000148‐88), STARTRK‐1 (NCT02097810), and STARTRK‐2 (NCT02568267)) were used. Adults (≥18 years) across trials were matched on available baseline characteristics. Outcomes evaluated included overall response rate (ORR), complete response (CR) rate, duration of response (DoR), overall survival (OS), progression-free survival (PFS), any serious treatment‐related adverse events of grade ≥ 3 (TRAEs), and TRAEs leading to treatment discontinuation. The MAIC included 74 patients from entrectinib trials and 117 and 147 patients for the larotrectinib efficacy and safety populations, respectively. Post‐matching, larotrectinib was associated with a significantly longer median duration of OS than entrectinib (p < 0.05) and a numerically longer median PFS (p = 0.07). ORR was similar for both agents (p = 0.63). The CR rate was higher (p < 0.05) and the DoR was longer for larotrectinib (p < 0.05). Safety outcomes were comparable and low for both treatments. Results were consistent in sensitivity analyses. These findings suggest favorable efficacy for larotrectinib and comparable safety profiles versus entrectinib in treating tropomyosin receptor kinase fusion cancer