GRACE :: Lung Cancer

maintenance therapy

Denise Brock

Lung Cancer Video Library – Timing Of Discussion Of Maintenance Therapy In First Line Treatment for Lung Cancer

Share

 

GRACE Cancer Video Library - Lung

 

H. Jack West, MD
President & CEO, GRACE

 

We are pleased to have GRACE’s Jack West, MD, Medical Director, Thoracic Oncology Program, Swedish Cancer Institute in Seattle, Washington, and President and CEO of GRACE bring 2017 updates to our Lung Cancer Video Library.  

In this latest video, Dr. West discusses advances in NSCLC –  Timing Of Discussion Of Maintenance Therapy In First Line Treatment for Lung Cancer


 

 

 

 

How Did You Like This Video?

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


 We would like to thank the following companies for their support of this program

 

                

 

 

                        

 

 
 

 

 


  


Denise Brock

Lung Cancer Video Library – Spanish Language: Video #6 What is maintenance therapy and why would it be recommended in advanced NSCLC?

Share
 
GRACE Cancer Video Library - Lung

 

For our 6th 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 is maintenance therapy and why it would be recommended 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
 

¿Cuál es la terapia de mantenimiento? Y ¿Por qué se recomienda en el cáncer pulmonar de células no pequeñas en etapa avanzada?

La terapia de mantenimiento consiste en extender la administración de quimioterapia más allá del tratamiento inicial. Los oncólogos normalmente administramos una quimioterapia de inducción, combinamos doblete de platino con un agente de tercera generación para tener la mayor tasa de respuesta y un mayor control de la enfermedad de manera precoz.

Sin embargo, no somos capaces de administrar más de 4 a 6 ciclos de quimioterapia por las toxicidades tardías que podrían hacer, limitando así el uso de quimioterapia, aunque el tumor no deje de crecer. El punto aquí es saber si mantener una terapia más suave será capaz de mantener en control la enfermedad en mayor tiempo, es decir, la administración seguida de quimioterapia puede prolongar el control de la enfermedad.

Hay 2 tipos de mantenimiento: el contenido, que consiste en bajar la intensidad de los fármacos, es decir, quitar alguno de los fármacos que estaba recibiendo (normalmente de 2 a 3 fármacos lo reducimos de 1 a 2) y la terapia cruzada que consiste en cambiar el fármaco que estábamos administrando en la inducción, esta terapia también se ha denominado segunda línea precoz porque lo que hacemos es anticipar una progresión con el uso de un nuevo mecanismo de acción con otra quimioterapia.

Recientemente, la terapia de mantenimiento ha mostrado de manera consistente una prolongación del tiempo libre de progresión, es decir, los pacientes que reciben terapia de mantenimiento están durante más tiempo con la enfermedad controlada. No sabemos si eso al final repercute en una mayor supervivencia porque al final muchos pacientes consiguen recibir terapias sucesivas que son muy eficaces. No todos los pacientes son candidatos a recibir la terapia de mantenimiento. Sobre todo se reserva a pacientes que no han tenido efectos secundarios durante la primera línea de tratamiento y quieren obtener el máximo beneficio de una quimioterapia de primera línea para tener la enfermedad más controlada. Sin embargo, hay pacientes que no han tolerado muy bien el tratamiento y han tenido toxicidades y quizás desean un periodo de vacaciones de quimioterapia. En estos pacientes se recomienda en cualquier caso un seguimiento estrecho para detectar de manera precoz una progresión.

Normalmente los agentes de quimioterapia de mantenimiento más utilizados en primera línea de mantenimiento contenido son: para los pacientes que reciben platino con pemetrexed se continua tras 4 ciclos, si hay enfermedad estable o respuesta parcial un tratamiento de pemetrexed cada 3 semanas de manera indefinida. Aquellos pacientes que están recibiendo la triple combinación de carboplatino, paclitaxel y bevacizumab reciben bevacizumab de mantenimiento.

También hay estudios en donde se ve el mantenimiento de gemcitabina cuando es cisplatino-gemcitabina la primera línea. Todos estos estudios demuestran que prolongar la quimioterapia mejora los tiempos libres a la progresión. Algunos estudios de terapias cruzadas, fundamentalmente son docetaxel o erlotinib como primera línea de terapia con otros agentes. Aquí existen más dudas porque lo que estamos haciendo, quizás sea adelantar una segunda línea precoz, y si hiciéramos un seguimiento más exhaustivo de los pacientes que no reciben quimioterapia podríamos tratarlos más exitosamente.

En cualquier caso, la recomendación de la terapia de mantenimiento no se debe de universalizar, se debe de discutir individualmente con cada paciente y su familia, no se debe de aceptar el uso de terapia de mantenimiento de manera generalizada. No todos los pacientes se benefician, los pacientes más indicados son aquellos que no han tenido toxicidades durante la inducción, desean un mayor control de la enfermedad y están dispuestos a venir de manera más regular a hacerse análisis de sangre en el hospital y recibir el tratamiento.


 

What is maintenance therapy? And, why is it recommended in non-small cells lung cancer in advanced stage?

Maintenance therapy consists in extending the administration of chemotherapy beyond the initial treatment. Oncologists usually administrate an induction chemotherapy, we also combine platinum doublets with a third generation agent to obtain a better response and control of the disease in an early stage.

However, we are not capable of administrating more than 4 to 6 cycles of chemotherapy because of late toxicities, so chemotherapy is limited even though the tumor does not stop growing. The key is to know if keeping a mild therapy will be able to control the disease for longer time.

There are 2 type of maintenance therapies: the continuation maintenance in which you decrease the intensity of drugs (from 2 to 3 drugs and reduce it to 1 or 2), and the switch maintenance therapy in which you change the drug. Switch maintenance is a second line approach because what we do is anticipate a progression with the use of a new mechanism in another chemotherapy.

Recently, maintenance therapy has shown consistently a prolongation of free progression time, which means that patients in maintenance therapy are more time with a controlled disease. We don’t know if this will affect the survival rate because at the end, some patients get successive therapies that are very effective. Not all patients are candidates to maintenance therapy. It is mostly reserved for patients who have not had side effects during first line treatment and want greater benefits from a first line chemotherapy and their disease more controlled. But, there are patients who have not tolerated the treatments and have had toxicities and they might want a vacation from chemotherapy. In these patients, we recommend to get a close follow up to detect an early progression.

The most used first line maintenance chemotherapy treatments are: for patients with platinum and pemetrexed it continues for 4 cycles, if there is a stable disease or a partial response to treatment, it should be pemetrexed every 3 weeks indefinitely. Those patients that are getting a triple combination of carboplatin, paclitaxel and bevacizumab receive bevacizumab as maintenance.

There are also studies where maintenance is with gemcitabine when cisplatin-gemcitabine are first line. All these studies show that prolonging chemotherapy improves the free progression time. Some switch maintenance therapy studies include docetaxel or erlotinib as first line with other agents. Here are more doubts because this approach might involve an early advance to second line, and if we made closer follow up, patients without chemotherapy could be treated successfully.

In any case, the recommendation in maintenance therapy should not be universalized, it must be discussed individually with each patient and their family. Not all patients get benefits, so the more suitable are those that have not had toxicities during induction, they want a more controlled disease or are willing to come regularly to get a blood test and treatment.

 


GRACE Video

Platinum-Based Doublets As the Cornerstone of First Line Treatment

Share
GRACE Cancer Video Library - Lung

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.

Download Transcript

How Did You Like This Video?

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

 

Transcript

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 is Maintenance Therapy for Advanced NSCLC?

Share
GRACE Cancer Video Library - Lung

GCVL_LU-F11_Maintenance_Therapy_Advanced_NSCLC

 

The concept of maintenance therapy for advanced lung cancer has emerged over the past few years. Dr. Jack West, medical oncologist, reviews the concepts behind it and treatment options for patients.

Download Transcript

How Did You Like This Video?

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

 

Transcript

One of the core ideas in treating advanced non-small cell lung cancer is that we try to treat is aggressively, early on, to induce the greatest shrinkage we can, which tends to be associated with a longer survival for patients. This specifically means that we typically treat with a two, or sometimes three-drug combination as first-line therapy, and most of the time, when we see tumor shrinkage, it tends to be front-loaded, and we see that early on, in the first one or two scans done. Most commonly, we’ll give four to six cycles of treatment for patients with this multi-drug combination, and then think about stopping treatment or downshifting. This idea of downshifting to a less intensive therapy, but still keeping something going, is the idea of maintenance therapy.

GCVL_LU-F11_Maintenance_Therapy_Advanced_NSCLC.001

So what is maintenance? It is essentially to maintain the tumor shrinkage that we achieved early on, with first-line therapy, but by using a more tolerable, less intensive regimen after that, that can be continued longitudinally, without too many cumulative side effects.

There are two main ways of approaching this — one is by doing what’s called continuation maintenance. You start with a two-drug or three-drug combination, and then you drop one or two of the agents off, and keep some of the first-line therapy going, but not all of it, and this makes it less intensive, and potentially able to be given for a much longer period of time to maintain the response that was achieved early on. An alternative approach is called switch maintenance, and that is starting with four to six cycles of a combination, then stopping all of those agents and switching to one or more agents after that, that have not been given before. Again, the idea is to come up with a regimen that is not too intensive, but that can maintain the momentum that was already achieved — basically keeping the tumor shrunk for longer.

Now, what do we hope to achieve by maintenance therapy? Several studies have demonstrated that there is a very consistent improvement in progression-free survival, the time before the cancer will progress, in patients who receive effective maintenance therapy. In just about all of the cases of what we call effective maintenance therapy, this is a treatment that is essentially a standard second-line treatment, but we give it earlier than second-line, which is when the patient has actually demonstrated progression of their cancer; instead, we’re giving it more proactively — immediately after first-line, and these agents that have been shown to improve survival when given second-line, after progression, are also associated with improvement in progression-free survival, and in some cases, significant improvement in overall survival when given earlier on, as a maintenance therapy.

However, there are some potential issues and questions about how necessary maintenance therapy really is, and although it is certainly a widely practiced approach and a standard of care, it is not a mandate at this point. This is because — the fact is that, the studies that give maintenance therapy do have an imbalance, where more of the patients on randomized maintenance therapy received more intensive therapy than the patients who are randomized to receive supportive care, or no treatment, just placebo perhaps, instead, at the time of completing first-line therapy. So, what we actually see is, sometimes it may just be that more treatment is associated with better outcomes, and longer survival, than less treatment. But, one thing we can say is that maintenance therapy assures us that the patients who have achieved tumor shrinkage, or at least stable disease, and are therefore the patients most likely to benefit from later treatment, definitely get that later therapy that can help them.

One of the challenges and issues about taking breaks from treatment is that some patients will decline and not be well enough to receive additional treatment that would have otherwise helped them if they had just gotten it earlier. So, with some patients potentially falling off the curve, missing that opportunity, there is a tendency to try to push effective treatment to earlier, and minimize time off of therapy where we might have patients miss that opportunity if they decline quickly.

So, that is the general approach to maintenance therapy — it is not a mandate, but it is something that we tend to individualize for our patients, and discuss whether they feel up to tolerating more treatment after going through four to six cycles of a combination first-line therapy, and whether they need to have a break, whether they want to go on a family vacation, etc.; there’s always room for individualizing, but for many patients, continuing with maintenance therapy — either continuation, or sometimes switch maintenance to a new therapy, may be a very appropriate approach.


Dr West

Transitioning Survival from Months to Years in Advanced NSCLC

Share

This is a slide presentation I did last week at a local conference, describing the steady, incremental improvements in survival with advanced/metastatic non-small cell lung cancer (NSCLC) that have occurred over the past 10-15 years.  There are still many pessimists who highlight that we haven’t cured metastatic lung cancer or most other advanced cancers, but I would contend that it is quite meaningful to be able to tell a patient with cancer that your treatment is quite likely to improve their survival and that, because of it, an ever-growing proportion of patients are living years with it, rather than the expectation of months that prevailed several years ago. 

This presentation highlights a couple of key developments:

1) More patients are receiving more lines of effective therapy. For patients with responsive cancer (unfortunately not everyone with advanced NSCLC), survival is improved not just with first line but also with later lines of treatment. Approaches like maintenance therapy and routine use of second line and later therapy translates to far more patients living beyond a year, sometimes well into the range of years, even independent of molecular markers.

2) A growing minority of patients are found to have a cancer that appears “driven” by a key biomarker for which we have a proven or potential target. Starting with EGFR mutations, seen in about 10% of NSCLC patients in North America, and then ALK rearrangements in another 4-5%, we’ve since added ROS1 and are looking at additional potentially fruitful targets like BRAF, HER2, and others.  These responses tend to be dramatic and prolonged. Even if the responses lasting years are only available to a minority of patients, we are adding to that minority year after year.

Of note, this slide deck does NOT cover immunotherapy. In part, this is because these strategies still have undefined, unproven benefit.  In addition, immunotherapy for lung cancer was the subject of a separate talk, and I did not want to encroach on that topic.

Here’s the presentation. I hope you find it thought-provoking and encouraged that we’re making progress, even if it can never be fast enough.

 

Transitioning Survival from Months to Years in Advanced Non-Small Cell Lung Cancer from H. Jack West

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