GRACE :: Lung Cancer

Search cancerGRACE.org

metastatic NSCLC

Denise Brock

Lung Cancer Video Library – Spanish Language: Video #4 What is the role of Avastin (bevacizumab) in treating advanced NSCLC today?

Share
 
GRACE Cancer Video Library - Lung

 

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?

 

 

 


 

How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.


 

TRANSCRIPTS – Spanish and English
download transcripts
 

¿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.

 


Denise Brock

Lung Cancer Video Library – Spanish Language: Video #3 How does the NSCLC subtype (histology) alter chemotherapy recommendations in advanced NSCLC?

Share
 
GRACE Cancer Video Library - Lung

 

For our third 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 how NSCLC subtype (histology) can alter chemotherapy recommendations in advanced NSCLC.

 

 

 


 

How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.


 

TRANSCRIPTS – Spanish and English
download transcripts
 

¿Cómo los subtipos histológicos del cáncer pulmonar de células no pequeñas alteran las recomendaciones en el estadio avanzado?

Los patólogos se han convertido en un aliado principal a los oncólogos para el tratamiento del cancer de pulmón. Antiguamente, clasificábamos el cancer de pulmón en dos grandes grupos: cancer microcítico de pulmón y cancer no microcítico de pulmón. El no microcítico de pulmón, que es el más frecuente actualmente en países occidentales, en 85% de los casos se subdivide en los subgrupos histológicos: adenocarcinoma (el más frecuente), escamoso y células grandes.

Hasta hace poco, el subtipo histológico no tenía ninguna influencia en el tipo de quimioterapia administrada porque todos los pacientes lo hacían parecido con los esquemas que teníamos. Sin embargo, en los últimos años han aparecido agentes de quimioterapia en los que se han visto ciertas ventajas según el tipo histológico. En primer lugar, en el adenocarcinoma, que es el subtipo más frecuente, el tratamiento de elección de primera línea suele ser pemetrexed en combinación con cisplatino.

Aunque en general no hay grandes diferencias entre la combinación de cisplatino con otros agentes de quimioterapia, un análisis posterior que comparaba cisplatino-pemetrexed vs cisplatino-gemcitabina no mostraba diferencias en la población global, pero al analizar por su grupo histológico se vio que los pacientes que tenían histología de adenocarcinoma o de células grandes, tenían resultados mejores que aquellos que tenían histología epidermoide. De hecho, los pacientes que tenían histología de epidermoide tenían mejores resultados cuando recibían cisplatino y gemcitabina en vez de cisplatino-pemetrexed. Por tanto desde aquel estudio nosotros, los oncólogos, necesitamos que los patólogos nos informen sobre el tipo histológico porque puede impactar en la supervivencia de los pacientes. Para la histología escamosa, en carcinoma epidermoide, no hay grandes diferencias en cualquiera de los esquemas de quimioterapia. Tanto lo taxanos como el paclitaxel y el docetaxel o la vinorelbina o los anti metabolitos tipo gemcitabina, obtienen resultados parecidos. Si bien, a través de ese ensayo clínico antes mencionado, cisplatino-gemcitabina suele ser el esquema que se utiliza en la actualidad.

El análisis de un estudio que comparaba la combinación de carboplatino y paclitaxel de manera trisemanal vs carboplatino y abraxane (paclitaxel unido a albúmina), se vio que los pacientes del subgrupo de histología epidermoide tenían una mejoría en los resultados sobre el paclitaxel. No se puede dar una recomendación a estas alturas porque es un análisis retrospectivo no dedicado y habría que confirmarlo de una manera prospectiva en un ensayo más grande, pero desde luego es una alternativa que los pacientes con carcinoma epidermoide de pulmón pueden tener.

En pacientes con histologías neuroendocrinas, esto es con diferenciación de células que tienen una producción de péptidos y que vienen de unas células especiales de la cresta neural, se les trata normalmente como si fuera un carcinoma microcítico. Su comportamiento biológico es más agresivo que el resto de tumores no microcítico. Está en el espectro de tumores neuroendocrinos de alto grado y las combinaciones de platino con etopósido se prefieren sobre el resto de combinaciones porque tiene una tasa de respuesta mayor, y en pacientes que tienen cancer de pulmón con histología neuroendocrina preferimos el uso de etopósido en primera línea, si bien, otras combinaciones son también aceptables.

La quimioterapia también la utilizamos en pacientes que tienen alteraciones histológicas. Hay datos que nos dicen que pacientes que tienen adenocarcinoma con translocación de ALK se benefician de quimioterapia con pemetrexed, sobre otras quimioterapias. La inmunoterapia, que de momento ha demostrado un incremento de supervivencia cuando se utiliza en segundas líneas y sucesivas, es especialmente útil en pacientes que tiene histologías de cancer epidermoide de pulmón. Aunque también, hemos visto que aumenta la supervivencia con histología no escamosa, pero la histología escamosa es la que más se beneficia de añadir inmunoterapia en segundas y terceras líneas de tratamiento.

En general, las quimioterapias tienen que ser consensuadas entre los oncólogos por los resultados del patólogo. Necesitamos buenos patólogos que nos digan que tipo histológico se tiene para poder optimizar y personalizar el uso de la quimioterapia.


 

How can the histological subtypes of non-small cell lung cancer alter the recommendations in advanced stage?  

Pathologists have become a principal ally to oncologists for lung cancer treatment. We used to classify lung cancer into two big groups: microcytic lung cancer and non-microcytic lung cancer. In the non-microcytic lung cancer, which is the most frequent in occidental countries, 85% of cases subdivide in histological subgroups: adenocarcinoma (most frequent), squamous and large cells.

Until recent, the histological subgroups did not have any influence in the type of chemotherapy selected because all patients had a very similar kind of treatment. However, in the last couple of years’ new agents have appeared in which there are certain advantages depending on the histology. First of all, in adenocarcinoma (most frequent), the first line treatment of choice is usually pemetrexed combined with cisplatin. 

In general, there are no big differences between combination of cisplatin with other chemotherapy agents. A recent comparative analysis between cisplatin-pemetrexed vs cisplatin-gemcitabine did not showed differences in global population, but when the analysis of histological group was done, it was observed that patients with adenocarcinoma or large cells histology had better results than those with epidermoid histology. In fact, patients with epidermoid histology had better response when they received cisplatin and gemcitabine instead of cisplatin-pemetrexed. Thus, we as oncologists need pathologists to inform about the histological features because it can impact in the patient’s survival. For squamous histology in epidermoid carcinoma there are no big differences in the chemotherapies used. Several drugs like taxanes: paclitaxel and docetaxel, vinorelbine and anti-metabolites like gemcitabine get very similar results. Nowadays, based on the clinical trial discussed, cisplatin-gemcitabine is usually the chosen treatment.

In a comparative analysis between the combination of carboplatin-paclitaxel three times a week and abraxane (paclitaxel bind to albumin), patients from the epidermoid subgroup had a better improvement in the results over paclitaxel. So far, we cannot give a recommendation based on this, because this was a retrospective not dedicated analysis, and to be used, it would have to be confirmed prospectively in a bigger trial, however; it is still an alternative that epidermoid carcinoma patients could have.

In patients with neuroendocrine histologic features, which is a differentiation of cells that produce peptides and come from the neural crest, the approach is as it was a microcytic carcinoma. Its biological behavior is far more aggressive than the rest of the microcytic tumors. Since it is in the high stage of neuroendocrine tumors a combination of cisplatin with and etoposide is preferred than the rest of the higher response combinations. In patients with lung cancer and neuroendocrine histology, we preferred a first line etoposide, but other combinations are accepted.

Chemotherapy is also used in patients with histological malignances. There is data that proves that patients with adenocarcinoma and translocation of ALK beneficiate from chemotherapy with pemetrexed over others. Immunotherapy has shown an increase of survival when is used as second line treatment, especially in lung cancer patients with epidermoid histology.

In general, chemotherapies have to be consensual between oncologists based on the pathologists’ results. We need great pathologists that can tell us the histological type to optimize and personalize the use of chemotherapy.

 


Dr West

How do we manage a “mixed response” to lung cancer treatment?

Share

Here’s a brief video that explains my approach to a so-called “mixed response” to treatment for a lung cancer.  

There isn’t a formal teaching or “best answer” about how to approach this issue, but what I explain here is a common and I think very sensible strategy for a still controversial clinical setting (if I do say so myself).  I’d welcome your comments.

Continue reading


Dr Pennell

Does it Matter Which Chemo Agent You Get with Your Platinum? Maybe it does…

Share

For years it has been generally accepted that the choices for the second drug in a platinum doublet for treating metastatic non-small cell lung cancer (NSCLC) were pretty much interchangeable. The question of whether cisplatin is better than carboplatin is a separate question, one which GRACE’s own Dr. Sanborn recently reviewed quite nicely. For the second drug, as long as the choice was a “newer generation” drug, oncologists would mix and match cisplatin or carboplatin with Taxol (paclitaxel), Taxotere (docetaxel), Gemzar (gemcitabine), or Navelbine (vinorelbine) based mostly upon which drug they liked the best or had the most experience with.

This perception that the specific second drug was irrelevant was not just pulled out of a hat; there has been reason to think they are all equally good. The most often quoted study to make this point has to be the ECOG 1594 trial (Comparison of Four Chemotherapy Regimens for Advanced Non–small-cell lung cancer), which randomized NSCLC patients to one of 4 arms: cisplatin/Taxol, carboplatin/Taxol, cisplatin/Gemzar, and cisplatin/Taxotere. The survival curves were essentially identical (see below), as were the response rates of the tumors.

ECOG 1594

Continue reading


Dr Pennell

A Case of a 36 Year-Old Never-Smoking Woman with Metastatic Adenocarcinoma of the lung

Share

With all this recent talk about never-smokers with lung cancer, and the interest in stories of patients with so-called “oligometastatic” cancer (minimal metastatic burden to perhaps a single site), I thought I would describe a recent case in my clinic as an illustration of how I use this information in everyday decision making.

Mrs. D, a very fit 36 year-old woman with a young child at home, presented to her family doctor last year with back pain. It didn’t seem to be getting better, so her doctor ordered an x-ray of the back which showed a very nasty-looking spot in the lower spine. An MRI confirmed that there was a large tumor in the lower spine, and a surgeon went in and took a piece of the bone to determine the cause. The result was a metastatic adenocarcinoma, with special tests pointing to a primary site from the lung.

She had never smoked, nor had her spouse. A PET scan showed a very small spot in her lung, with no evidence of spread to local lymph nodes, and no evidence of metastatic disease outside of the single metastasis in the spine. An orthopedic surgeon opined that she probably could resect the entire vertebrae involved, but this would be a major undertaking.

This type of case, aside from the heartbreaking anguish of having to tell a young mother she has lung cancer, causes all of us in the oncology world fits. How could such a small tumor, less than 1cm in size, be the cause of the spine tumor? Was it worthwhile to discard what we intellectually know about metastatic lung cancer (incurable) and treat her aggressively for cure, and if so would we be putting her through Hell only to make ourselves feel better about not giving up on such a young patient?

Continue reading


Ask Us, Q&A
Lung/Thoracic Cancer Expert Content

Archives

Share

GRACE Cancer Video Library - Lung Cancer Videos

 

2015_Immunotherapy_Forum_Videos

 

2015 Acquired Resistance in Lung Cancer Patient Forum Videos

Share

Join the GRACE Faculty

Breast Cancer Blog
Pancreatic Cancer Blog
Kidney Cancer Blog
Bladder Cancer Blog
Head/Neck Cancer Blog
Share

Subscribe to the GRACEcast Podcast on iTunes

Share

Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon

Subscribe to
GRACE Notes
   (Free Newsletter)

Other Resources

Share

ClinicalTrials.gov


Biomedical Learning Institute

peerview_institute_logo_243