GRACE :: Lung Cancer

PDL1

Denise Brock

Lung Cancer Video Library – PDL1 as a Biomarker for Second Line

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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 exciting new advances in NSCLC –  PDL1 as a Biomarker for Second Line.

 


 

 

 

 

 

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Denise Brock

Lung Cancer Video Library – PDL1 As A Biomarker For First Line

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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 exciting new advances in NSCLC –  PDL1 as a Biomarker for First Line.  

 


 

 

 

 

 

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

How Important is the Impact of Smoking Cessation on Survival?

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WCLC_2015_D_How_Important_Impact_Smoking_Cessation_Survival

 

Drs. Ben Solomon, Leora Horn, & Jack West review impressive data demonstrating a striking survival improvement from successful efforts at smoking cessation among smokers undergoing lung cancer CT screening.

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Transcript

Dr. West:  Finally, there’s a fair bit — we cover a lot of ground at the World Conference on Lung Cancer, and one of the topics that I think is good to have gotten airplay is smoking cessation, and tobacco interests and policy. I was surprised, and it was sobering to see a presentation at the Presidential Symposium that suggested that smoking cessation efforts, in the process of lung cancer screening, makes a bigger interest — has a bigger impact on patient survival, not necessarily from lung cancer, but potentially from cardiovascular issues, than picking up lung cancer. Were there things about the smoking cessation discussions during this meeting that had an impact for you, or that you found particularly surprising?

Dr. Solomon:  I’m not surprised with those findings, I think smoking has a huge range of detrimental health effects, even outside lung cancer — other types of cancer, as you pointed out, cardiovascular disease as well, and I think it’s important to have strong smoking cessation measures, both at the levels of doctors and patients, but also as a society, and at a governmental level. In Australia, we’ve recently introduced plain paper packaging of cigarettes, so instead of having very attractive, different colored cigarette boxes, the government has chosen that the nastiest shade of green, sort of a puke-colored, green-brown color, to wrap cigarette packets in now. Tobacco companies are taking the government to court because they know that it will impact on sales, but I think those sorts of measures together with, as unpopular as it may be, taxes on tobacco, are things that have real impacts on smoking rates in the population, and in young people.

Dr. West:  Yeah, absolutely. It turns out the biggest impact you can have is raising taxes, especially in young smokers. Your thoughts — anything to add?

Dr. Horn:  So, I think what Australia is doing is incredible, and I remember hearing about it at the last meeting. You know, the study that they presented with smoking cessation screening — the problem is, most patients who are being screened are over age 55, so they’ve been smoking for thirty years. And so, you know, the more that we can do to stop young people from ever starting is really going to be the key to reducing smoking-related cancers.

Dr. West:  Thank you so much for joining me.

Dr. Solomon: Thanks, Jack.

Dr. Horn: Thanks, Jack!


GRACE Video

Should PD-L1 Testing Be Ordered at Diagnosis or After Progression?

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WCLC_2015_PD-L1_Testing_Ordered_Diagnosis_After_Progression

 

Drs. Leora Horn, Ben Solomon, & Jack West consider the factors that might lead us to favor testing for PD-L1 at initial workup of a patient with advanced NSCLC or after progression.

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Transcript

Dr. West:  What about the timing of PD-L1 testing? We’re used to doing testing for various biomarkers at the time of initial diagnosis, and I think that it may be a barrier if you have a patient who’s progressing now, with multiple new liver lesions and a new adrenal metastasis, to then have to go send them to interventional radiology, wait a few weeks for the result, and potentially not start your second line therapy choice until a month or more later. I think this was a particular issue when they were trying to look at PD-L1 in relapsed small cell, where a lot of the patients were progressing too fast to act on the results. So, is PD-L1 testing likely to be a barrier, particularly in the setting of previously treated, and now progressing, patients?

Dr. Horn:  So, there was data at this meeting suggesting that there’s fairly good concordance between initial diagnosis and testing at the time of — some of these patients were tested for entry on study; I don’t think that is as much a barrier as the initial trials — you couldn’t test pleural effusions, you couldn’t test FNAs, it had to be core biopsies, and many lung cancer patients are diagnosed off an FNA or a pleural effusion…

Dr. West:  FNA being, fine needle aspirate.

Dr. Horn:  Fine needle aspirate, and so, how do you interpret those results? But, if you have an initial biopsy that’s PD-L1 positive, the data seems to suggest that, for the most part, that remains even at the time of progression on chemotherapy.

Dr. West:  That’s certainly important — what’s your sense of this, that it’s, really, early or not bother?

Dr. Solomon:  I think we’re to think about PD-L1 as a biomarker in a different way than we think about EGFR mutations or ALK gene rearrangements. So, EGFR mutations and ALK rearrangements we think of present, right from the beginning, they’re an essential part of the tumor — when we talk about tumor heterogeneity, we describe them as being in the trunk of a branching tree. But, PD-L1 is potentially a dynamic thing, and I think it’s reassuring to see the concordance data that was presented by, I think it was a Genentech group that presented that data, between biopsies taken at different times or at different places in the same patient. But we’ve also seen sections of tumors that have some parts that stain positive for PD-L1, and others that are negative, which does raise concern about how much we can believe one particular result. So, I think it’s, again, an unresolved question.

Dr. West:  Again, early days still, there’s still much more to learn.


GRACE Video

Do You Order PD-L1 Testing Before Choosing an Immune Checkpoint Inhibitor?

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WCLC_2015_Order_PD-L1_Testing_Before_Choosing_Immune_Checkpoint_Inhibitor

 

Drs. Ben Solomon, Leora Horn, & Jack West consider how valuable testing for PD-L1 expression is in clinical practice and whether it should be integrated in clinical decision making around immunotherapies.

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Transcript

Dr. West:  One of the key differences that we’re seeing, is really, the strategy that the different companies take in terms of just different denominators, patient populations, and that some are, like nivolumab, is being largely tested in unselected populations looking at PD-L1 levels, or not looking at PD-L1 levels, while several of the other agents in this space are really being restricted to patients who are PD-L1 positive, and seem to, in most of the trials, have a better probability of long response. Do you see PD-L1, now, as an important biomarker that you would use if it’s not mandated — for instance, say, in the nivolumab patients with non-squamous disease?

Dr. Horn:  So, nivolumab, for first line, they are looking at PD-L1. So, when we’re talking about second or third line, with the squamous data, you know, I think a big part of the issue is, is tissue even available for testing? And if there is, which cut point do you use? We’ve even watched with atezolizumab, that cut points changed from their original phase one data, it was 5-10% and now we’re up to 50% cut point. So, right now the data suggests that you can use nivolumab regardless of PD-L1 status, it’s approved regardless of PD-L1 status, and so, that’s the way we’re doing it now. Our hospital is in the process of setting up PD-L1 testing, but it’s not there yet, and, so, the question is, if you are going to use the drug, which assay are you going to send out for, because there are different assays, and which commercial company are you going to send it to — the PD-L1 is a bit of a mess, and it requires a lot of work for us to sort out what to do.

Dr. West:  So Ben, where do you think we are now, and where are we going to be in a few years with this?

Dr. Solomon:  Yes, so look, I think what’s clear is that PD-L1 does enrich for a group of patients that are more likely to benefit. But I think what’s equally clear is that, if a patient is PD-L1 negative, there’s still a chance that they can benefit from treatment with a PD-1 or a PD-L1 inhibitor. So, this strategy of using PD-L1 to enrich for a group of patients who might want to, for example, use a PD-1 axis inhibitor for the first line, probably does make sense, but it probably doesn’t make sense to exclude a patient based on PD-L1 negativity, and the issues that Leora raised about which antibody to use, what lab to get the tests done in, what the cutoff is, absolutely — those are completely unresolved, and who is to know whether a PD-L1 result that you get from a private laboratory has any sort of relationship to the very rigorous, robust PD-L1 testing that’s done in the clinical trials.


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