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Denise Brock

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

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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?

 

 

 


 

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TRANSCRIPTS – Spanish and English
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¿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?

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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.

 

 

 


 

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TRANSCRIPTS – Spanish and English
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¿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.

 


GRACE Video

How Rate of Progression Can Affect Treatment Decisions

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GCVL_LU-F03_Progression_Rate_Affect_Treatment_Decisions

 

Dr. Benjamin Levy, Mount Sinai Health Systems, explains how the rate of progression of a patient’s cancer may affect treatment choices.

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I think we know a lot now about how to treat patients with advanced stage lung cancer, and there are several things that we factor in when we treat patients. One is clearly the genetic makeup of their tumor — we tend to look at this when we’re trying to decide on a targeted drug for these patients. The other is perhaps histology, looking at a particular type of lung cancer whether it be adenocarcinoma or squamous cell, and deciding what type of chemotherapy we’re going to give. One that I would also like to mention that’s sometimes factored into treatment decisions is the variability of the aggressiveness of the tumor, meaning that some lung cancers can be very aggressive, and despite popular belief, some can be quite indolent.

Now while most lung cancers are thought to be more aggressive, I have come across many patients with lung cancers that tend to grow less rapidly, and the thought is: how do we factor this in when we’re making treatment decisions? I think the variability of progression plays out in two clinical scenarios.

One is a patient who is on chemotherapy or even on a targeted drug who’s doing well and tolerating the drug, and in which we are ordering scans every six to twelve weeks and we’re seeing that the tumor is growing but at a very limited pace, and the question is: if the patient is tolerating the chemotherapy or the targeted drug, should that limited pace of growth trigger a treatment change? I would say in our practice, not necessarily. Sometimes if growth is small, or growth is limited, or the pace is limited, sometimes we will keep patients on that particular therapy. My thought is they’re probably deriving some sort of benefit from that therapy if they’re tolerating it.

I think the other scenario where this plays out is for a patient who perhaps hasn’t been tolerating therapy and is on a treatment break. Sometimes not all patients tolerate chemotherapy and may need a treatment break, particularly when they get to maintenance, and the question becomes: if the cancer is growing on scans while they’re on a treatment break, should you reinstitute the drug or even reinstitute another drug? Again, I think that depends on how quickly things are moving along — for patients who may have not tolerated treatment well who are on a treatment break and their cancer is growing very, very slowly, I think it’s reasonable to continue to watch them as long as they understand that the cancer may grow rapidly at some point.

So I think these are important considerations when you’re treating a patient, not only to look at the genetic alterations in the tumor, not only to look at histology, but also to consider the natural evolution of this cancer and how it’s moving, and how quickly it’s growing when making treatment decisions.


GRACE Video

Platinum-Based Doublets As the Cornerstone of First Line Treatment

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GCVL_LU-F02_Platinum_Doublets_First_Line_Treatment

 

Dr. Benjamin Levy, Mount Sinai Health Systems, discusses platinum-based chemotherapy as the standard of care for advanced NSCLC patients without targetable genetic mutations.

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I’m going to be talking about the role of platinum chemotherapy for patients with advanced stage non-small cell lung cancer. No doubt, there have been significant advances in the past ten years with the development of targeted drugs for those patients who have a particular genetic makeup of their tumor. Many of these drugs have shown to be quite effective for those patients that are susceptible to such treatments. I think what we know though is unfortunately many patients will not have the genetic alterations that make them eligible for targeted treatments, and we have to default to chemotherapy.

I think ‘default’ is a bit of a misnomer because platinum chemotherapy or platinum doublet chemotherapy remains a standard of care for patients with advanced stage lung cancer who don’t harbor particular genetic alterations in their lung cancer and that’s okay. I think what we know about chemotherapy, platinum chemotherapy specifically, is that this type of approach improves survival for patients and it also can have the potential to improve quality of life as well as control symptoms as they relate to the lung cancer. So all three of those measures can be achieved with platinum chemotherapy.

Now chemotherapy comes in a variety of different shapes and sizes — the chemotherapy that we tend to use sometimes is called histology-directed chemotherapy, so patients with a particular type of lung cancer called adenocarcinoma may get one type of platinum chemotherapy, whereas patients with a particular type of lung cancer called squamous cell may get a different type of chemotherapy.

I just want to speak briefly about maintenance chemotherapy for adenocarcinoma patients. This is the most common type of lung cancer we see, and again for those patients that don’t harbor genetic alterations that make them eligible for targeted drugs, we can offer a very effective chemotherapy that’s also very tolerable and that can also be given as a maintenance strategy. What I mean by that is that patients generally get four cycles of chemotherapy and for those patients that at least achieve stable disease after their four cycles and are tolerating treatment, I think that we have good data now that we can drop the platinum and continue one of the drugs called pemetrexed and provide a survival advantage for those patients. There are certain maintenance strategies that are also being looked at in the squamous cell population and there are studies ongoing for that.

I think, in some, that the chemotherapies we have now work very well, they can extend life, they can improve quality of life and they’re well tolerated, and I also think specifically for the subset of patients that come in with adenocarcinoma or non-squamous, that there should be a consideration for patients who are tolerating chemotherapy to be offered a maintenance approach.


GRACE Video

What are the Goals of Treating Advanced NSCLC?

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GCVL_LU-F01_Goals_Treating_Advanced_NSCLC

 

Dr. Benjamin Levy, Mount Sinai Health Systems, lists the goals of treating advanced NSCLC and the methods used to achieve those goals.

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I think there are several goals when treating a patient with advanced non-small cell lung cancer. For one I think we want to extend life, two is I think we want to palliate symptoms, and three is I think we want to improve quality of life. So all three of those goals are achievable, I think, with the therapies that we have right now.

Now, some of these therapies are targeted drugs, so for patients that have genetic alterations or a genetic makeup that makes them eligible for targeted drugs, then clearly we can offer these drugs and I think we can achieve all three of those goals. But even for patients without genetic alterations, and patients who will not be receiving targeted drugs, I think we can extend life, improve quality of life and palliate symptoms by delivering chemotherapy. I think we know now that chemotherapy is not the chemotherapy of the days of old — these drugs are given in combination, are tolerable and can improve outcomes. We also have now immunotherapy, and so all three types of systemic approaches can help achieve these three goals.

In addition to these three goals, I think it’s important that we also have goals of care discussions with patients from the being of treatment. I think what that means is that we really come up with what the shared expectations are for treatment. Patients may ask specific questions like “how many months will additional chemotherapy give me versus no chemotherapy?” I think these questions are fair game. I think we can certainly talk about averages but also tell patients that they’re not an average and I would sway doctors or patients receiving information not to stick to exact numbers, but I do think that a goals of care discussion upfront is very important.

That brings into the realm the role of palliative approaches or palliative care. Many patients feel that palliative care is hospice or end of life care, but this is not the case. I think what we know now is that patients who have early palliative care referrals to palliative care specialists in conjunction with their treatment, specifically for lung cancer patients, these patients actually live longer.

So I bring up this whole concept of discussing goals of care very early on so we can make sure that our patients are referred to palliative care specialists who can treat patents alongside us and work in conjunction to help improve outcomes for our patients.


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