Source Text
Existe un interés creciente en el uso de biopsias líquidas, sin embargo, los datos sobre análisis longitudinales del ADN tumoral circulante (ADNct) siguen siendo relativamente limitados. En este trabajo se presenta un análisis longitudinal de este, en un ensayo de fase Ib que evalúa la eficacia y seguridad de ribociclib más terapia endocrina (TE), en pacientes asiáticas con cáncer de mama avanzado, con receptor hormonal positivo (HR+) y receptor 2 del factor de crecimiento epidérmico humano negativo (HER2-).
Participaron 87 pacientes en total, 58 japonesas premenopáusicas y postmenopáusicas y 29 asiáticas no japonesas postmenopáusicas. Todas recibieron ribociclib más TE (letrozol, fulvestrant, o tamoxifeno con goserelina).
Se analizaron 574 muestras utilizando un panel de secuenciación de nueva generación dirigido a 572 genes asociados a cáncer, y se correlacionaron según la mejor respuesta general (BOR).
El tratamiento con ribociclib más TE disminuyó el ADNct, desde el inicio, en la mayoría de las pacientes, independientemente de la dosis o el esquema de TE. Las participantes con respuesta parcial y enfermedad estable tenían un ADNct más bajo, respecto a las que presentaban progresión tumoral (ADNct alto); estos niveles se mantuvieron hasta el final del tratamiento. Por otro lado, en la mayoría de las mujeres con respuesta parcial y enfermedad estable con progresión posterior, el ADNct aumentó al final del ensayo.
Al inicio del estudio se determinaron los genes alterados con mayor frecuencia, dentro de estos se incluyeron PIK3CA (29%) y TP53 (22%). Las pacientes con alteraciones en estos genes presentaron una mediana de supervivencia libre de progresión más corta, en comparación con las que tenían ambos genes del tipo no mutante.
En conclusión, los niveles de ADNct al inicio del estudio se correlacionaron con la supervivencia libre de progresión, y los aumentos de ADNct durante el tratamiento permitieron la identifcación de la enfermedad progresiva en una fracción significativa de pacientes antes de que fuera detectada mediante métodos radiológicos. Los resultados demuestran el potencial de medir el ADNct durante el tratamiento, para identificar la progresión tumoral y las alteraciones genéticas que tengan implicaciones clínicas.
DeepL
There is growing interest in the use of liquid biopsies, however, data on longitudinal analysis of circulating tumor DNA (ctDNA) remain relatively limited.
This paper presents a longitudinal analysis of this in a phase Ib trial evaluating the efficacy and safety of ribociclib plus endocrine therapy (ET) in hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) Asian patients with advanced breast cancer.
A total of 87 patients participated, 58 premenopausal and postmenopausal Japanese and 29 postmenopausal non-Japanese Asian patients. All received ribociclib plus ET (letrozole, fulvestrant, or tamoxifen with goserelin).
A total of 574 samples were analyzed using a next-generation sequencing panel targeting 572 cancer-associated genes, and correlated by best overall response (BOR).
Treatment with ribociclib plus ET decreased ctDNA, from baseline, in the majority of patients, regardless of dose or ET schedule.
Participants with partial response and stable disease had lower ctDNA than those with tumor progression (high ctDNA); these levels were maintained until the end of treatment. On the other hand, in the majority of women with partial response and stable disease with subsequent progression, ctDNA increased at the end of the trial.
At baseline, the most frequently altered genes were determined, including PIK3CA (29%) and TP53 (22%). Patients with alterations in these genes had a shorter median progression-free survival compared to those with both genes of the non-mutant type.
In conclusion, ctDNA levels at baseline correlated with progression-free survival, and increases in ctDNA during treatment allowed identification of progressive disease in a significant fraction of patients before it was detected by radiological methods. The results demonstrate the potential of measuring ctDNA during treatment to identify tumor progression and genetic alterations that have clinical implications.
Matecat
There is growing interest in the use of liquid biopsies, however, data on longitudinal analyzes of circulating tumor DNA (ctDNA) remain relatively limited.
This work presents a longitudinal analysis of this, in a phase Ib trial that evaluates the efficacy and safety of plus endocrine therapy (ET), in Asian patients with advanced breast cancer, with positive hormone receptor (HR+) and receptor human epidermal growth factor 2 negative (HER2-).
A total of 87 patients participated, 58 premenopausal and postmenopausal Japanese women and 29 postmenopausal non-Japanese Asian women. All received ribociclib plus TE (letrozole, fulvestrant, or tamoxifen with goserelin).
574 samples were analyzed using a next-generation sequencing panel targeting 572 cancer-associated genes and correlated by best overall response (BOR).
Treatment with ribociclib plus TE decreased ctDNA, from baseline, in the majority of patients, regardless of the dose or TE regimen.
Participants with partial response and stable disease had lower ctDNA compared to those with tumor progression (high ctDNA); these levels were maintained until the end of treatment. On the other hand, in the majority of women with partial response and stable disease with subsequent progression, ctDNA increased at the end of the trial.
At the beginning of the study, the most frequently altered genes were determined; these included PIK3CA (29%) and TP53 (22%). Patients with alterations in these genes had a shorter median progression-free survival compared to those with both genes of the non-mutant type.
In conclusion, ctDNA levels at baseline were correlated with progression-free survival, and increases in ctDNA during treatment allowed the identifcation of progressive disease in a significant fraction of patients before it was detected by radiological methods. The results demonstrate the potential of measuring ctDNA during treatment to identify tumor progression and genetic alterations that have clinical implications.