RESUMEN
BACKGROUND: Larotrectinib is approved for patients with metastatic TRK fusion cancers, including differentiated thyroid (DTC), colorectal cancer (CRC), and soft tissue sarcoma (STS). Given the basket clinical trial design of larotrectinib, direct comparisons against standard of care in each of the mentioned cancers have not been assessed. Also, owing to the limited duration of follow-up in clinical trials, long-term outcomes for treatments are generally not known or estimated. OBJECTIVE: To compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with metastatic DTC, CRC, and STS who are eligible to receive larotrectinib against patients with unknown NTRK gene fusion status receiving standard-of-care therapy. METHODS: We developed a partitioned survival model to estimate the long-term comparative effectiveness of larotrectinib and standard of care for 3 tumor types. Larotrectinib survival data, assessed by independent review committee, were derived from an updated July 2020 analysis of 19, 8, and 23 adult patients (aged ≥ 18 years) with metastatic TRK fusion DTC, CRC, and STS, respectively. The DTC survival data also included 2 patients aged less than 18 years for a total of 21 patients. Survival estimates for standard of care were derived from published clinical trials. Progressionfree and overall survival for all treatments were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Lognormal) fit to the available data. The final exponential form was selected based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the preprogression and postprogression health states by utility weights derived from publicly available literature. RESULTS: Patients receiving larotrectinib experienced more LYs and QALYs compared with those receiving standard-of-care treatments across all 3 assessed cancer types. In DTC, patients receiving larotrectinib had 7.15-8.26 additional LYs (5.87-6.12 QALYs); in CRC, patients receiving larotrectinib had 1.26-1.27 additional LYs (1.00 QALYs); and in STS, patients receiving larotrectinib had 5.56 additional LYs (1.99 QALYs). CONCLUSIONS: Compared with standard of care in metastatic TRK wild-type cancers, larotrectinib is estimated to result in improved LY and QALY outcomes based on parametric extrapolations of intrial survival data. Because patient-level data were unavailable for adjusted analyses, a cross-trial comparison was performed. Given the limitations of this analytic approach and the small sample size for larotrectinib in trials, future studies should reassess the comparative effectiveness of larotrectinib vs standard of care as treated patients accrue and long-term survival data mature. DISCLOSURES: K. Suh, J. Carlson, and S. Sullivan report consulting fees from Bayer US LLC. F. Xia and T. Williamson are employees of Bayer US LLC. This study was funded by Bayer US LLC. The sponsor had no role in the design of the study and did not have any role in the execution, analyses, interpretation of the data, or decision to submit results.
Asunto(s)
Neoplasias Colorrectales , Sarcoma , Adulto , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Humanos , Pirazoles , Pirimidinas , Años de Vida Ajustados por Calidad de Vida , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Nivel de Atención , Glándula TiroidesRESUMEN
La Candida haemulonii forma parte de la especie Candida no albicans. La candidemia por C. haemulonii es sumamente infrecuente, pero mortal, en los recién nacidos. Se informa sobre los dos primeros recién nacidos con candidemia por C. haemulonii en China tratados con fluconazol y se revisan dos artículos informados con anterioridad. Nuestro informe incrementa la sensibilización sobre la candidemia por C. haemulonii en recién nacidos críticos y resalta la importancia de un diagnóstico y un tratamiento tempranos de esta infección mortal.
Candida haemulonii forms part of the non-albicans Candida species. The candidemia caused by C. haemulonii is extremely rare but fatal in neonates. We reported the first two neonates with C. haemulonii candidemia in China which were treated with fluconazole and reviewed two papers previously reported. Our report adds further awareness on C. haemulonii candidemia in critical neonates and points out the importance of an early diagnosis and treatment of this fatal infection.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Fluconazol/uso terapéutico , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Candidemia/tratamiento farmacológico , Candida/aislamiento & purificación , China , Resultado del Tratamiento , Infecciones Relacionadas con Catéteres/microbiología , Candidemia/etiología , Candidemia/microbiología , Antifúngicos/uso terapéuticoRESUMEN
Candida haemulonii forms part of the non-albicans Candida species. The candidemia caused by C. haemulonii is extremely rare but fatal in neonates. We reported the first two neonates with C. haemulonii candidemia in China which were treated with fluconazole and reviewed two papers previously reported. Our report adds further awareness on C. haemulonii candidemia in critical neonates and points out the importance of an early diagnosis and treatment of this fatal infection.
La Candida haemulonii forma parte de la especie Candida no albicans. La candidemia por C. haemulonii es sumamente infrecuente, pero mortal, en los recién nacidos. Se informa sobre los dos primeros recién nacidos con candidemia por C. haemulonii en China tratados con fluconazol y se revisan dos artículos informados con anterioridad. Nuestro informe incrementa la sensibilización sobre la candidemia por C. haemulonii en recién nacidos críticos y resalta la importancia de un diagnóstico y un tratamiento tempranos de esta infección mortal.