Article and Video CATEGORIES
For our 4th video in the GRACE Spanish Lung Cancer Library, Antonio Calles, MD, Medical Oncologist, Thoracic Oncology Program, Hospital General Universitario, Gregorio Marraron, Madrid, Spain joined GRACE to discuss what the role of Avastin (bevacizumab) is in treating advanced NSCLC today?
TRANSCRIPTS - Spanish and English
¿Cuál es el rol de Avastin (bevacizumab) en el tratamiento del cáncer de pulmón de células no pequeñas en la actualidad?
Bevacizumab es un anticuerpo monoclonal dirigido contra VEGF (factor de crecimiento endotelial vascular) una proteína que secreta los tumores para aumentar la producción de vasos sanguíneos. Los tumores, como cualquier otra célula del organismo, necesitan nutrientes, glucosa, oxígeno y para eso necesita crear vasos sanguíneos para que le llegue ese suplemento a las células tumorales. Bevacizumab atrapa la proteína soluble y hace disminuir la vasculatura tumoral, normaliza esa vasculatura y permite una mejor entrada de los fármacos de quimioterapia dentro del tumor.
Bevacizumab se ha asociado a quimioterapia en primera línea de cancer de pulmón, en combinación con dobletes de platino. Los estudios demuestran que añadir Bevacizumab a la quimioterapia, aumenta la supervivencia de los pacientes que reciben este tratamiento. El ensayo clínico E4599 comparo la administración de carboplatino y taxol durante 4 ciclos cada 3 semanas vs la misma combinación en donde se añadía el antiangiogénico Bevacizumab continuado de Bevacizumab de mantenimiento. La adición de Bevacizumab a la quimioterapia, mejoraba los resultados y supervivencia de los pacientes.
Sin embargo, en el desarrollo precoz de este fármaco, se observó un aumento de sangrado y de efectos secundarios con riesgo vital. Fundamentalmente correspondía a tumores con histología epidermoide, tumores centrales, cavitados, invadían grandes vasos o había sangrados inicialmente como es la hemoptisis (expulsar sangre con la tos). En el estudio fase 3, estos pacientes fueron excluidos, por tanto, la aprobación de Bevacizumab se limitó a pacientes con histología de adenocarcinoma o histologías no escamosas en las que no hubiera invasión vascular, hemoptisis significativa o cualquier otro riesgo de sangrado relevante. De hecho, la aprobación de Bevacizumab está limitada para pacientes porque puede detener la cicatrización de las heridas y puede producir perforación intestinal y sangrados. Esto hace que la mayor parte de los pacientes con cancer de pulmón en primera línea, no pueda recibir Bevacizumab.
Aproximadamente se calcula que el 30% de los pacientes, en un practica regular, pueden llegar a recibir Bevacizumab por aquellas contraindicaciones de histología, afectación vascular y riesgo de sangrado, pero en aquellos pacientes que pueden recibir la combinación con Bevacizumab puede aumentar los resultados de la quimioterapia y se debe de recomendar a esto pacientes añadir Bevacizumab a la quimioterapia.
Recientemente se han aprobado otros fármacos en segundas líneas en combinación con quimioterapias, demostrando un beneficio de añadir anti-angiogénicos como ranibizumab y vandetanib, en segundas líneas. El concepto es que la angiogénesis en cáncer de pulmón funciona, si bien se prefiere utilizarlo en primera línea para obtener el máximo beneficio.
English TRANSCRIPT
Bevacizumab is a monoclonal antibody special against VEGF (vascular endothelial growth factor), a protein that is secreted by tumor to increase the productions of blood vessels. The tumors, as any other cell, need nutrients, glucose and oxygen, so it needs to create new blood vessels to get the nutrients. Bevacizumab catches the soluble protein and stops the tumoral vasculature, it normalizes it and allows a better drug entry to the tumors.
Bevacizumab has been associated to first line lung cancer chemotherapy in combinations with platinum doublets. Studies have shown that adding bevacizumab to chemotherapy increases survival of patients. The clinical trial E4599 compared the use of carboplatin and taxol for 4 cycles every 3 weeks against the addition of the anti-angiogenic bevacizumab continuing bevacizumab as maintenance. The addition of bevacizumab to chemotherapy improved the results and survival of patients.
However, in the early development of this drug it was observed an increase of bleeding and other side effects with vital risk. It fundamentally included tumors with epidermoid histology, central and cavitary tumors, they invaded big vessels or cause bleedings like hemoptysis (bleeding cough). In the phase 3 of this study, these patients were excluded, so the approval of bevacizumab was limited to patients with adenocarcinoma or non-squamous histology in which there was no vascular invasion, hemoptysis, or any other risk of bleeding. These findings made that most patients with first line lung cancer cannot use bevacizumab.
About 30% of patients in a regular practice, can receive bevacizumab for the histological conditions, vascular affectations and bleeding risk, but those who can receive bevacizumab can increase the results of chemotherapy. It should be recommended to these patients to add bevacizumab to their chemotherapy.
Recently, there has been an approval of other second line drugs in combination with chemotherapy, it proved great benefits of adding anti-angiogenic drugs like ranibizumab and vandetanib. The concept is that angiogenesis in lung cancer works, so it should be recommended as first line to obtain maximal benefits.
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