RESUMO
BACKGROUND: Older patients with HER2-positive metastatic breast (HER2 + MBC) cancer are underrepresented in clinical trials. We aim to describe the treatment patterns and overall survival (OS) for older women receiving trastuzumab for HER2 + MBC. METHODS: Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for Australian women ≥ 65 years initiating trastuzumab for HER2 + MBC between 2003 and 2015. We describe time-on-trastuzumab; type and timing of other cancer treatments; rates of cardiac monitoring; and OS from trastuzumab initiation for HER2 + MBC. RESULTS: Of 5404 women initiating trastuzumab for HER2 + MBC, 1583 (29%) were ≥ 65 years old, and the proportion of older patients increased from 20% in 2003 to 38% in 2015. The median age for older women was 73 years and 516 (33%) were ≥ 75 years. Most older patients (92%) received ≥3medicines for comorbidities other than cancer. Median (IQR) time on trastuzumab was 14.1 months (5.9-32.1) and on all chemotherapy was 5.6 months (3.3-10.8). 74% received ≥1 chemotherapy agent and 56% received endocrine therapy. Half (49%) of patients had a cardiac assessment prior to initiating trastuzumab and overall 1228 (76%) had ≥1 cardiac assessment during the study period. At a median follow-up of 6 years, 73% of patients had died and the median OS was 25.6 months (IQR 10.7-58.7). CONCLUSIONS: Older patients comprise a growing proportion of patients treated with HER2-targeted therapies in the real-world but they remain underrepresented in trials of these agents. Few trials report duration or OS estimates for older patients but our estimates are similar to those from trials that have. Although cardiac monitoring was a requirement of accessing trastuzumab during our study period, many patients did not undergo a cardiac assessment.
Assuntos
Neoplasias da Mama/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Vigilância da População , Receptor ErbB-2/genética , Estudos Retrospectivos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/efeitos dos fármacos , Resultado do TratamentoRESUMO
Introdução: O câncer de mama é o mais comum entre as mulheres em todo o mundo, representando quase 25% de todos os casos de câncer. Alguns fármacos possuem características peculiares relacionadas à cardiotoxicidade. Objetivo: Analisar a incidência, as características clínicas e os fatores de risco associados à ocorrência de cardiotoxicidade em pacientes submetidas ao protocolo doxorrubicina e ciclofosfamida seguido ou não de taxanos e naquelas que realizaram o mesmo protocolo associado ao trastuzumabe. Método: Trata-se de um estudo de coorte realizado em um hospital público do Rio de Janeiro. Foram incluídas 153 pacientes que iniciaram tratamento entre os meses de setembro e novembro de 2012. A cardiotoxicidade foi definida com base nos critérios do Cardiac Review and Evaluation Committee e da Sociedade Brasileira de Cardiologia. Foi calculado o risco relativo (RR), utilizando-se um intervalo de confiança (IC) de 95%. Resultados: A incidência de cardiotoxicidade foi de 17%. Observou-se queda da fração de ejeção do ventrículo esquerdo em 31,3% e 52,2% das pacientes nos grupos human epidermal growth factor receptor-type 2 (HER-2) negativo e positivo, respectivamente. Foram identificados três casos de insuficiência cardíaca, sendo dois em pacientes HER-2 positivas. As pacientes que utilizaram trastuzumabe apresentaram maior risco de desenvolver cardiotoxicidade (RR=3,53; IC 95%: 1,84-6,79) em comparação com as mulheres do grupo HER-2 negativo. Conclusão:Foi possível verificar a ocorrência de casos de cardiotoxicidade em ambos os grupos com maior incidência para o grupo HER-2 positivo.
Introduction: Breast cancer is the most common among women worldwide, accounting for almost 25% of all cancer cases. Some drugs have a peculiar characteristic related to cardiotoxicity. Objective: Analyze the incidence, clinical characteristics and risk factors associated with cardiotoxicity in patients undergoing protocol doxorubicin and cyclophosphamide followed or not by taxanes and in those who underwent the same protocol associated with trastuzumab. Method: Cohort study conducted in a public hospital in Rio de Janeiro. 153 patients were included between September and November 2012. Cardiotoxicity was defined based on the criteria of the Cardiac Review and Evaluation Committee and the Brazilian Society of Cardiology. The relative risk (RR) was calculated using a 95% confidence interval (CI). Results: The incidence of cardiotoxicity was 17%. Left ventricular ejection fraction decreased in 31.3% and 52.2% of the patients in the negative and positive human epidermal growth factor receptor-type 2 (HER-2) groups, respectively. Three cases of heart failure were identified, two in HER-2 positive patients. Patients using trastuzumab had a higher risk of developing cardiotoxicity (RR=3.53; CI 95%: 1.84-6.79) compared to women in the HER-2 negative group. Conclusion: It was possible to verify the occurrence of cases of cardiotoxicity in both groups with higher incidence for the HER-2 positive group.
Introducción: El cáncer de mama es el más común entre las mujeres en todo el mundo, y representa casi el 25% de todos los casos de cáncer. Algunos medicamentos tienen característica peculiar relacionada con la cardiotoxicidad. Objetivo: Analizar la incidencia, las características clínicas y los factores de riesgo asociados con la cardiotoxicidad en pacientes sometidos al protocolo doxorrubicina y ciclofosfamida seguidos o no por taxanos y en aquellos que se sometieron al mismo protocolo asociado con trastuzumab. Método: Este es un estudio de cohorte realizado en un hospital público en Río de Janeiro. Se incluyeron 153 pacientes que comenzaron el tratamiento entre septiembre y noviembre de 2012. La cardiotoxicidad se definió según los criterios del Comité de Revisión y Evaluación Cardíaca y la Sociedad Brasileña de Cardiología. El riesgo relativo (RR) se calculó utilizando un intervalo de confianza (IC) del 95%. Resultados: La incidencia de cardiotoxicidad fue del 17%. La fracción de eyección del ventrículo izquierdo disminuyó en el 31,3% y el 52,2% de los pacientes en los grupos human epidermal growth factor receptor-type 2 (HER-2) negativo y positivo, respectivamente. Se identificaron tres casos de insuficiencia cardíaca, dos en pacientes con HER-2 positivo. Los pacientes que usaban trastuzumab tenían un mayor riesgo de desarrollar cardiotoxicidad (RR=3,53; IC 95%: 1,84-6,79) en comparación con las mujeres en el grupo negativo HER-2. Conclusión: Fue posible verificar la aparición de casos de cardiotoxicidad en ambos grupos con mayor incidencia para el grupo HER-2 positivo.
