ABSTRACT
RESUMEN Objetivo. Nuestro objetivo fue estudiar la eficacia y la seguridad de trastuzumab-emtansina (T-DM1) en comparación con otras terapias anti-HER-2 en el cáncer de mama (CM) HER-2 positivo. Materiales y métodos. Realizamos un metaanálisis de red (NMA, por sus siglas en inglés) de ensayos clínicos aleatorizados (ECA). Nuestro estudio se centró en pacientes sometidos al tratamiento para el cáncer de mama localmente avanzado no resecable (CMLA) o cáncer de mama metastásico (CMm), que incluía esquemas con trastuzumab y taxanos. Además, consideramos casos dentro de los primeros 6 meses de tratamiento para el cáncer de mama temprano (CMT) HER-2 positivo. Resultados. Se incluyeron en nuestro análisis un total de 23 ECA y 41 reportes. En CMLA y CMm, no se observaron diferencias estadísticamente significativas en ninguna de las comparaciones entre T-DM1 y otras terapias anti-HER-2 positivo. Al evaluar la sobrevida libre de progresión (SLP), trastuzumab-deruxtecan (T-DXd) y PyroCap demostraron una mayor eficacia en comparación con otros tratamientos (Hazard Ratio [HR]: 3,57; intervalo de confianza al 95% [IC 95%]: 2,75-4,63 y HR: 1.82; IC 95%: 1,35-2,44; respectivamente), mientras que T-DM1 por sí solo mostró una efectividad superior en comparación con LapCap (HR: 0,65; IC 95%: 0,55-0,77), TrasCap (HR: 0,65; IC 95%: 0,46-0,91), LapCapCitu (HR: 0,60; IC 95%: 0,33-1,1), Nera (HR: 0,55; IC 95%: 0,39-0,77) y Cap (HR: 0,37; IC 95%: 0,28-0,49). Conclusiones. Este NMA estableció un ranking basado en la eficacia y seguridad comparativas entre las intervenciones disponibles. Aunque superior a otros esquemas, T-DM1 mostró una menor eficacia en la SLP y la tasa de respuesta objetiva, y una tendencia hacia una sobrevida global peor que T-DXd.
ABSTRACT Objective. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2 therapies in HER2+ breast cancer (BC). Materials and Methods. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC). Results. A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44; respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49). Conclusions. NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance in PFS and overall response rate and a trend towards worse overall survival than T-DXd.
ABSTRACT
Objective To detect the expression of HER2 in clinical colon carcinoma tissue ,to investigate its correlation with the clinicopathological characteristics and to analyze its influence on the proliferation and cell cycle in colon carcinoma cell lines .Methods 108 specimens of colon carcinoma and corresponding paracancerous tissues were collected .The hybridization in situ and real-time quantitative polymerase chain reaction were used to detect the HER 2 expression in those specimens .The relationship between HER2 expression and the clinicopathologic features was analyzed .The expression of HER2 in colon carcinoma cells(SW480 and Lo-Vo) was reduced by using the antisense technology .The MTT assay and the flow cytometry were used to investigate the HER2 in-fluences on the cell proliferation and cell cycles .Results The hybridization in situ results showed that the HER2 positive expres-sion rate was 66 .67% in colon carcinoma and 10 .19% in the paracancerous tissues ,the difference between them was statistically significant(P<0 .05) .The real-time fluorescent quantitative PCR results further showed that HER2 was found to be overexpressed in 61 .11% of the colon carcinoma tissue(P<0 .05);the expression of HER2 was gradually increased with the progress of colon cancer .(P<0 .05);the expression of HER2 in the colon tissue with lymph node metastasis was also significantly higher than that without lymph node metastasis in colon carcinoma (P<0 .05);siRNA-HER2 could significantly reduce the expression of HER2 in colon cancer cell lines(SW480 and LoVo) ,the growth of colon carcinoma cell lines was also significantly inhibited and the propor-tion of cells in G0/G1 phase was increased ,while the proportion of cells in S phase and G2/M phase was decreased .Conclusion HER2 is closely related with the occurrence and development of colon carcinoma ,its mechanism could regulate the grow th of colon carcinoma cells via mediating the transition of G1/S phase ,which may provide a new target for the treatment of colon carcinoma .