Abemaciclib as adjuvant treatment for high-risk early breast cancer / Abemaciclib en adyuvancia para el tratamiento del cáncer de mama precoz de alto riesgo

Objective: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorization (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. Method: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label, and multicenter phase III study. A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1–3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67≥20%. Patients were randomized (1:1) to receive adjuvant abemaciclib+endocrine therapy (n = 2808) or endocrine therapy alone (n = 2829) for 2 years, with endocrine therapy prescribed for at least 5 years. Results: With a median follow-up of 15.5 months, abemaciclib+endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598–0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%), and diarrhea (7.8% vs. 0.2%). Conclusions: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for...(AU)

Objetivo: Adaptar el informe GHEMA de abemaciclib, un inhibidor de quinasas dependientes de ciclinas 4 y 6, con autorización de la Agencia Europea del Medicamento en abril de 2022 para el tratamiento adyuvante de pacientes adultos con cáncer de mama precoz, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo, con afectación ganglionar y riesgo elevado de recaída; en combinación con hormonoterapia. Método: La eficacia y seguridad de abemaciclib se evaluó en un estudio fase III multicéntrico, aleatorizado y abierto. Se incluyeron 5.637 pacientes diagnosticados de cáncer de mama precoz con ganglios positivos, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo y alto riesgo de recaída. El criterio de alto riesgo se definió como la presencia de ≥ 4 ganglios positivos, o de 1–3 ganglios y al menos una de las siguientes características: tamaño del tumor ≥5 cm, grado histológico 3 o Ki-67 ≥ 20%. Los pacientes fueron aleatorizados (1:1) a recibir durante 2 años abemaciclib + hormonoterapia (n = 2.808) u hormonoterapia sola (n = 2.829). En ambos brazos el tratamiento con hormonoterapia se mantuvo mínimo 5 años. Resultados: Con una mediana de seguimiento de 15,5 meses, abemaciclib + hormonoterapia mostró beneficio significativo frente a la hormonoterapia sola [HR = 0,747 (IC95% 0,598-0,932), p = 0,0096], con una mejora absoluta del 3,5% en la tasa de supervivencia libre de enfermedad invasiva a 2 los años. Este beneficio se mantuvo con una mediana de seguimiento de 27,7 meses, logrando una mejora en la tasa de supervivencia libre de enfermedad invasiva del 2,7% y del 5,4% a los 2 y 3 años, respectivamente. La incidencia de efectos adversos grado 3–4 fue superior en el brazo de abemaciclib (45,9% vs. 12,9%); e incluía neutropenia (19,6% vs. 0,8%), leucopenia (11,4% vs. 0,4%) y diarrea (7,8% vs. 0,2%). Conclusiones: Los resultados del ensayo pivotal son suficientes para considerar abemaciclib como...(AU)

Abemaciclib en adyuvancia para el tratamiento del cáncer de mama precoz de alto riesgo / Abemaciclib as adjuvant treatment for high-risk early breast cancer

Objective: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorization (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. Method: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label, and multicenter phase III study. A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1–3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67≥20%. Patients were randomized (1:1) to receive adjuvant abemaciclib+endocrine therapy (n = 2808) or endocrine therapy alone (n = 2829) for 2 years, with endocrine therapy prescribed for at least 5 years. Results: With a median follow-up of 15.5 months, abemaciclib+endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598–0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%), and diarrhea (7.8% vs. 0.2%). Conclusions: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for...(AU)

Objetivo: Adaptar el informe GHEMA de abemaciclib, un inhibidor de quinasas dependientes de ciclinas 4 y 6, con autorización de la Agencia Europea del Medicamento en abril de 2022 para el tratamiento adyuvante de pacientes adultos con cáncer de mama precoz, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo, con afectación ganglionar y riesgo elevado de recaída; en combinación con hormonoterapia. Método: La eficacia y seguridad de abemaciclib se evaluó en un estudio fase III multicéntrico, aleatorizado y abierto. Se incluyeron 5.637 pacientes diagnosticados de cáncer de mama precoz con ganglios positivos, receptor hormonal positivo, receptor del factor de crecimiento epidérmico negativo y alto riesgo de recaída. El criterio de alto riesgo se definió como la presencia de ≥ 4 ganglios positivos, o de 1–3 ganglios y al menos una de las siguientes características: tamaño del tumor ≥5 cm, grado histológico 3 o Ki-67 ≥ 20%. Los pacientes fueron aleatorizados (1:1) a recibir durante 2 años abemaciclib + hormonoterapia (n = 2.808) u hormonoterapia sola (n = 2.829). En ambos brazos el tratamiento con hormonoterapia se mantuvo mínimo 5 años. Resultados: Con una mediana de seguimiento de 15,5 meses, abemaciclib + hormonoterapia mostró beneficio significativo frente a la hormonoterapia sola [HR = 0,747 (IC95% 0,598-0,932), p = 0,0096], con una mejora absoluta del 3,5% en la tasa de supervivencia libre de enfermedad invasiva a 2 los años. Este beneficio se mantuvo con una mediana de seguimiento de 27,7 meses, logrando una mejora en la tasa de supervivencia libre de enfermedad invasiva del 2,7% y del 5,4% a los 2 y 3 años, respectivamente. La incidencia de efectos adversos grado 3–4 fue superior en el brazo de abemaciclib (45,9% vs. 12,9%); e incluía neutropenia (19,6% vs. 0,8%), leucopenia (11,4% vs. 0,4%) y diarrea (7,8% vs. 0,2%). Conclusiones: Los resultados del ensayo pivotal son suficientes para considerar abemaciclib como...(AU)

Abemaciclib as adjuvant treatment for high-risk early breast cancer.

OBJECTIVE: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorization (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. METHOD: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label, and multicenter phase III study. A total of 5637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive, and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1-3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67≥20%. Patients were randomized (1:1) to receive adjuvant abemaciclib+endocrine therapy (n = 2808) or endocrine therapy alone (n = 2829) for 2 years, with endocrine therapy prescribed for at least 5 years. RESULTS: With a median follow-up of 15.5 months, abemaciclib+endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone [HR = 0.747 (95% CI 0.598-0.932), P = 0.0096]; achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3 years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%), and diarrhea (7.8% vs. 0.2%). CONCLUSIONS: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for high-risk early breast cancer in highly selected patients. However, in order to the efficacy results present less uncertainty, we must wait for a evaluation later, in which we can have a mature determination at 3 years (with more patients at risk).

Abemaciclib as adjuvant treatment for high-risk early breast cancer. / [Artículo traducido] Abemaciclib en adyuvancia para el tratamiento del cáncer de mama precoz de alto riesgo.

OBJECTIVE: To adapt the GHEMA report of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6. European Medicines Agency authorisation (April 2022) includes, in combination with endocrine therapy, the adjuvant treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, early breast cancer at high risk of recurrence. METHOD: The efficacy and safety of abemaciclib were evaluated in a randomized, open-label and multicenter phase III study. A total of 5,637 patients diagnosed with early breast cancer with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive and high risk of recurrence were included. High risk was defined as patients with 4 or more positive axillary lymph nodes, or 1-3positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3 or Ki-67 ≥ 20%. Patients were randomized (1:1) to receive adjuvant abemaciclib + endocrine therapy (n = 2,808) or endocrine therapy alone (n = 2,829) for 2 years, with endocrine therapy prescribed for at least 5 years. RESULTS: With a median follow-up of 15.5 months, abemaciclib + endocrine therapy demonstrated a statistically significant improvement in invasive disease-free survival versus endocrine therapy alone (HR = 0.747 [95% CI 0.598-0.932], p = 0.0096); achieving an absolute improvement of 3.5% invasive disease-free survival rate at 2-years. These results were maintained, with a median follow-up of 27.7 months: absolute improvement of 2.7% and 5.4% in invasive disease-free survival rate at 2 and 3-years, respectively. All-causality grade 3 or 4 adverse events were 45.9% for abemaciclib and 12.9% for endocrine therapy, and included neutropenia (19.6% vs. 0.8%), leukopenia (11.4% vs. 0.4%) and diarrhea (7.8% vs. 0.2%). CONCLUSIONS: The results of the pivotal trial are sufficient to consider abemaciclib as adjuvant treatment for high-risk early breast cancer in highly selected patients. However, in order to the efficacy results present less uncertainty, we must wait for a evaluation later, in which we can have a mature determination at 3 years (with more patients at risk).

Revisión sistemática sobre la suplementación profiláctica de L-carnitina en la nutrición parenteral de recién nacidos pretérmino / A systematic review about prophylactic L-carnitine administration in parenteral nutrition of extremely preterm infants

Objetivo: Los recién nacidos pretérmino con nutrición parenteral total tienen tanto una reducción de la ingesta de L-carnitina como de las reservas tisulares, lo que podría suponer una peor tolerancia de los lípidos paren‑ terales. El objetivo fue revisar la literatura científica en busca de los posibles beneficios clínicos de su administración en la nutrición parenteral. Métodos: Revisión sistemática de los documentos recuperados en las bases de datos MEDLINE/Pubmed, Scopus, The Cochrane Library, British Library EThOS y TESEO. Los términos utilizados como descriptores fueron «Total Parenteral Nutrition» y «Carnitine». La calidad de los artículos se evaluó mediante la escala de Jadad. Resultados: Tras aplicar los criterios de inclusión y exclusión, se seleccionaron para la revisión 18 artículos de las 93 referencias recuperadas, de los cuales 4 fueron descartados al no ser considerados de alta calidad. Casi la totalidad de los estudios coincidían en las variables analíticas medidas (carnitina libre y acilcarnitina, triglicéridos, ácidos grasos libres y cuerpos cetónicos). Además, en algunos se tenían en cuenta otras variables clínicas, como la ganancia ponderal o la apnea. Conclusiones: La suplementación rutinaria en la nutrición parenteral de recién nacidos pretérmino sí parece mejorar los niveles plasmáticos de carnitina, pero sin llegar a demostrar una mejoría significativa en el perfil lipídico, ni aumento de la ganancia ponderal, ni disminución de la morbi-mortalidad o reducción de la estancia hospitalaria. Son necesarios más estudios para demostrar si la suplementación sistemática a recién nacidos pretérmino que requieren nutrición parenteral total durante más de un mes aportaría beneficios clínicos

Objective: Preterm infants with total parenteral nutrition are at particular risk of developing carnitine deficiency with impaired tolerance of parenteral lipids. The objective was to review the scientific literature on potencial benefits of prophylactic L-carnitine administration in parenteral nutrition of preterm newborns. Methods: Selected scientific articles in MEDLINE/PubMed, Scopus, The Cochrane Library, British Library EThOS and TESEO databases were assessed for this systematic review. The terms used as descriptors were «Total Parenteral Nutrition» and «Carnitine». Jadad scale was chosen to evaluate the quality of them. Results: 18 out of the 93 references retrieved were selected for reviewing after applying the inclusion and exclusion criteria, 4 of them were discarded for being considered of low quality. Almost all studies agreed on the analytical variables measured (free carnitine and acylcarnitine, triglycerides, free fatty acids and ketone bodies). Other clinical variables such as weight gain, apnea, or lenght of stay at hospital were also considered. Conclusions: The present results prove that routine supplementation in the parenteral nutrition of preterm newborns may help to increase carnitine levels, but neither a relevant improvement in the lipid profile, or an increase in weight gain, or a decrease in morbimortality or reduction of hospital stay could be demonstrated. More studies are needed in preterm infants to know whether routine supplementation of L-carnitine in neonates requiring total parenteral nutrition for a long time would provide any clinical benefit

A systematic review about prophylactic L-carnitine administration in parenteral nutrition of extremely preterm infants.

OBJECTIVE: Preterm infants with total parenteral nutrition are at particular risk of developing carnitine deficiency with impaired tolerance of parenteral lipids. The  objective was to review the scientific literature on potencial benefits of  prophylactic L-carnitine administration in parenteral nutrition of preterm  newborns. METHODS: Selected scientific articles in MEDLINE/PubMed, Scopus, The Cochrane Library, British Library EThOS and TESEO databases were assessed for this  systematic review. The terms used as descriptors were «Total Parenteral  Nutrition¼ and «Carnitine¼. Jadad scale was chosen to evaluate the quality of  them. RESULTS: 18 out of the 93 references retrieved were selected for reviewing after  applying the inclusion and exclusion criteria, 4 of them were discarded for being  considered of low quality. Almost all studies agreed on the analytical variables  measured (free carnitine and acylcarnitine, triglycerides, free fatty acids and  ketone bodies). Other clinical variables such as weight gain, apnea, or lenght of  stay at hospital were also considered. CONCLUSIONS: The present results prove that routine supplementation in the  parenteral nutrition of preterm newborns may help to increase carnitine levels,  but neither a relevant improvement in the lipid profile, or an increase in weight  gain, or a decrease in morbimortality or reduction of hospital stay could be  demonstrated. More studies are needed in preterm infants to know whether  routine supplementation of L-carnitine in neonates requiring total parenteral  nutrition for a long time would provide any clinical benefit.

Objetivo: Los recién nacidos pretérmino con nutrición parenteral total tienen tanto una reducción de la ingesta de L-carnitina como de las reservas tisulares, lo que podría suponer una peor tolerancia de los lípidos  parenterales. El objetivo fue revisar la literatura científica en busca de los  posibles beneficios clínicos de su administración en la nutrición parenteral.Métodos: Revisión sistemática de los documentos recuperados en las bases de  datos MEDLINE/Pubmed, Scopus, The Cochrane Library, British Library EThOS y  TESEO. Los términos utilizados como descriptores fueron «Total Parenteral  Nutrition¼ y «Carnitine¼. La calidad de los artículos se evaluó mediante la escala de Jadad.Resultados: Tras aplicar los criterios de inclusión y exclusión, se seleccionaron para la revisión 18 artículos de las 93 referencias recuperadas, de  los cuales 4 fueron descartados al no ser considerados de alta calidad. Casi la  totalidad de los estudios coincidían en las variables analíticas medidas (carnitina  libre y acilcarnitina, triglicéridos, ácidos grasos libres y cuerpos cetónicos).  Además, en algunos se tenían en cuenta otras variables clínicas, como la  ganancia ponderal o la apnea.Conclusiones: La suplementación rutinaria en la nutrición parenteral de recién  nacidos pretérmino sí parece mejorar los niveles plasmáticos de carnitina, pero  sin llegar a demostrar una mejoría significativa en el perfil lipídico, ni aumento  de la ganancia ponderal, ni disminución de la morbimortalidad o reducción de la  estancia hospitalaria. Son necesarios más estudios para demostrar si la  suplementación sistemática a recién nacidos pretérmino que requieren nutrición  parenteral total durante más de un mes aportaría beneficios clínicos.