GRACE :: Lung Cancer

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Denise Brock

Lung Cancer Video Library – 2017 The Changing Landscape of First Line Treatment for EGFR Mutation-Positive NSCLC

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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 the changing landscape of first-line treatment for EGFR mutation-positive non-small cell lung cancer (NSCLC).


 

 

 

 

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Denise Brock

Lung Cancer Video Library – 2017 Changing Standard of Care for Stage 3 Non-Small Cell Lung Cancer (NSCLC)

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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 the changing standard of care for stage 3 non-small cell lung cancer (NSCLC). 


 

 

 

 

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

 

                

 

 

                        

 

 
 

 

 


  


GRACE Video

Platinum-Based Doublets As the Cornerstone of First Line Treatment

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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.

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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

Chemoradiation as a Standard of Care for Unresectable NSCLC

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GRACE Cancer Video Library - Lung

GCVL_LU-E09_Chemoradiation_Standard_Care_Unresectable_NSCLC

 

Dr. Nasser Hanna, Indiana University Health, discusses the development of chemoradiation as a standard of care for unresectable stage III NSCLC.

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Transcript

So what is the standard of care treatment for those who are not going to have surgery for stage III disease that are either medically inoperable or they are surgically unresectable? Well for decades radiation therapy has formed the backbone of treatment. If you can’t surgically remove a tumor, you can certainly apply radiation to that tumor; you radiate the tumor, the lymph nodes, and some surrounding tissue where microscopic disease may be. That form of therapy can be effective but by itself oftentimes is not curative. It will shrink tumors and oftentimes patients will have a reduction in symptoms, maybe a tumor was compressing an airway or maybe it was causing them to cough up blood or something like that where the radiation therapy can be effective at relieving some of those symptoms.

Historically radiation therapy alone for stage III disease has resulted in about a 5% cure rate — the vast majority of patients will develop growth shortly thereafter, either outside the radiated field, occasionally in the radiated field, but most commonly distant metastatic disease. That’s because even though the disease appears to be confined to the chest, we know that the majority of patients already have microscopic spread of their cancer to other parts of their body. That’s not something that you can see on a CT scan, it’s not something that you can see on a PET scan, it’s certainly not something you can feel on a physical exam, but we know that’s the case because historically when you’ve done surgery alone for this group of patients and successfully removed all the disease you can see, the vast majority of people will still develop distant, recurrent disease usually within about a year’s time. Radiation therapy alone can have some effectiveness for patients, but by and large it’s a short term effect and it oftentimes doesn’t cure patients.

Starting really about three or four decades ago, chemotherapy was beginning to be incorporated in the treatment of patients with stage III disease. In the 1970s it was demonstrated that chemotherapy could shrink cancers that had already metastasized, and perhaps if it could shrink cancers that were large enough to see on x-rays, maybe it would be effective enough to treat that microscopic disease that patients have with stage III lung cancer.

So beginning in the 1970s and really going in full force in the 1980s, chemotherapy was incorporated with radiation strategies and a whole host of different strategies were tried. The most common strategy was to give a couple of courses of chemotherapy first, try to shrink the cancer, try to treat that microscopic metastatic disease early on, and then follow that with radiation therapy. Early efforts into that approach were not terribly successful, and that’s for several reasons. Number one, our staging tools weren’t very good, so oftentimes even though we thought patients have stage III disease, they oftentimes already had stage IV disease and they weren’t going to be cured with that type of strategy. Secondly, many patients who participated in those clinical trials were already not doing well. They had what we call a low performance status, in other words, they had already become very debilitated by their disease and their ability to tolerate therapy wasn’t very good. Thirdly, our radiation techniques were fairly crude at the time, radiation planning was very crude at the time as well. Fourth, our chemotherapy actually was not terribly active; although it was modestly active, it probably wasn’t the most effective therapy that patients could receive. Lastly, it really wasn’t recognized, the clinical significance of having weight loss. So oftentimes patients will have suffered a lot of weight loss which is really a signal that they truly have systemic disease, and when you include all those types of patients on clinical trials, you’re really setting yourself up for failure.

The initial attempts at trying to treat patients with both chemotherapy and radiation therapy really would be considered failures. Outcomes were not very good, we really didn’t seem to improve cure rates over radiation therapy alone, and this was in an era in which chemotherapy was not very well tolerated. That really started to change in the mid-1980s, and really a landmark trial was conducted by a United States cooperative group. In this trial, patients were excluded if they had a really poor functional status, if they had significant weight loss, and so it really narrowed the group of patients who could potentially benefit from this therapy. In this study, patients received two courses of chemotherapy, and then that was followed by six weeks of radiation therapy. For the first time, we were able to demonstrate an improvement in cure rates. It was fairly modest, we went from about a 5% cure rate to about a 15% cure rate.

Because that was the first time that was really ever demonstrated, a second trial was required to really make sure that this was a real finding. So a second trial was done in the United States by other cooperative groups; this was a much larger trial and they essentially replicated that data.

Well in the 1980s and in the 1990s, this strategy of giving chemotherapy and radiation therapy at the same time was becoming a standard approach in many different cancers. This included cancers of the pancreas, of the esophagus, of the head and neck, of the rectum, and so that sort of idea was attempted in lung cancer. Now we weren’t sure if we could actually give chemotherapy and radiation at the same time to somebody who had lung cancer. It’s a bit different radiating the mid-chest area where the heart is going to get radiation, the lungs are exposed to a lot of toxicity from radiation, the esophagus would oftentimes be in the field of radiation. So the first thing we had to do was prove that it was safe and feasible to do, and indeed investigators did demonstrate that. The next step was to determine whether that strategy of giving chemotherapy and radiation at the same time would truly be more effective than giving them separately – there were a lot of theoretical advantages to doing that. First, you would not delay the radiation therapy. Secondly, you might be able to give both therapies at the same time which would work to kill cancer cells in different ways simultaneously, but we knew that it would come at a risk.

We knew that it would come at a risk of increased side effects when you give the treatments together versus giving them separately. Several randomized trials were conducted in the United States, in Japan, in Europe, that looked at comparing the concurrent administration of chemotherapy and radiation to the sequential administration of those two. Those trials by and large demonstrated that while it was more difficult on patients and there were certainly more side effects, you could improve cure rates by giving the treatment concurrently.

So really through the 1990s and into the early 2000s, the standard of care treatment for those who were well enough and fit enough for this type of therapy was to give concurrent chemotherapy and radiation therapy.


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