Chapters Transcript Video Treatment Options for Limited Stage Small Cell Lung Cancer It's my pleasure to introduce Doctor Joseph Treat. Um who's going to talk to us about treatment options for limited stage uh lung cancer. Doctor Treat. He's a professor in the Department of Hematology Oncology, Vice Chair of uh education, Medical Director of Amity Care at Fox Chase. Um Doctor Treat was uh my attending when I first started as a fellow many, many moons ago at Fox Chase. So I still blame him for what I don't know about lung cancer. Um um over the past 2425 years, it's been more than just a mentorship. It's become a friendship, at least from my point of view. I don't know what he thinks and it is an absolute pleasure to have him here talking to us about this topic. Mm. As you saw a little bit earlier, uh, immunotherapy in advanced stage actually has pretty limited value compared to how well it does a non small cell which house is gonna go over in a few minutes. This is the earliest trials of single agent drug checkpoint inhibitor and in relapsed small cell and then, and the outcomes here are fairly modest in terms of pfs and even. Ok, what's going on there? It's still odd but uh I'll talk through it. So, and then you saw this trial just a moment ago. This is the first of, of a couple of different uh trials using a triplet immunotherapy chemotherapy versus chemotherapy alone, an extensive stage. And again, and hopefully it does better here, at least. Uh the, the median advantages here are modest. They're 2 to 3 months in all three trials of checkpoint plus chemo versus chemo. Certainly not what we saw a much more robust outcomes in nonsmall cell. And it was, has been pointed out just for just a few minutes ago. The five year survival with extensive stage with checkpoint is about 12% not the 30 35% we see in non small cell. So while there's additive value, it is, it is modest. And with that background, uh this trial was launched and I must say, uh at least speaking for myself, I wasn't predicting this trial would be terribly positive or maybe not even positive based on the modest benefits we saw in extensive stage. And that was the top line result uh released and then uh get into more of the detail of this trial. So this trial is practice changing one of the three or so trials that came out as o this year, which really changed standard of care and it's the default position now in terms of treatment and it really is based on the extensive stage uh data which again is modest and also at least from a strategic or conceptual point of view. It's based on the work in nonsmall cell uh with the checkpoint inhibitors that after chemo reds which is in stage three nonsmall cell, the the uh addition of maintenance checkpoint inhibitors made a profound difference. So there was good rationale for approaching this and this is the trial design. I'm not going to really spend any time on the third arm which has not yet been reported on. And there's other examples where doublet uh immunotherapies have not uh shown additional benefit. So we're just going to look at the uh at the main, the main stage, so to speak the the VMA versus placebo after chemo rads. OK. So this is limited stage patient. And there, there is a variable definition of what that means. A lot of it has to do with how well one can construct uh coherent radiation fields, uh baseline characteristics. I always think it's worth looking at these type of things, you know, they're pretty mundane, but they sometimes can tell you things about outcomes or explain why something happened or didn't happen. And once again, we see a as in all lung trials at a phase three level that of that are, you know, significant number size. The media age here is a decade, a full decade younger than the median age of this disease. A diagnosis a little better here on the female uh presence in the trial. And someone earlier in the morning commented on that we don't capture Vape data. Well, I I would argue we don't even capture smoking data very well. Uh Look at this, uh 8% are never smokers with small cell. We believe that I don't believe it. And I think we all had the experience that uh a never smoker uh by self patient, self definition is someone who quit smoking three packs a day, six weeks ago. So we don't, I'm being a little jocular here, but it's really uh we, we do a very poor job with documenting smoking history, let alone vaping. And we're at a point now, we're not too far off from the horizon of 20 years out from introduction of carcinogens causing lung cancer with vaping. So we need to get better at more granularity in this type of intake uh demographic. The rest of the things are quite well balanced. Now, people are still getting a lot of PC I, despite the uh controversy about it, it's a additive benefit. And uh I, I also draw your attention to the uh radiation. Although certainly the lung treating community firmly believes in B ID radiation. As you can see, it's not being uh incorporated universally and far from it, the majority of patients here got older style single fraction so daily. So, you know, things have not evolved and, and caught quite up with where we are with at least clinical trial data. Uh look at the uh the line here that talks about uh discontinuation of treatment and it's, it's definitely higher as you might expect in the uh in the treatment arm with the uh checkpoint inhibitor. So this is the bottom line and this is dramatic and I must say I was pleasantly surprised by this. Uh would not have thought the results would be this robust. It's a a really remarkable difference, almost doubling. When was the last time we saw a doubling of median survival? Unbelievable, but it is believable. And the hr here is quite, quite robust the 0.73. And very importantly, with the subgroup analysis, we can see no one subgroup hold the results either in a negative or or positive fashion. They all line up in the same direction. Yes, the, the CIS are crossed more than once. But still the, the uh point analysis is they're all positive and, and favor the uh the treatment with their vale. The other end point of PFS is they don't always follow, but they typically do follow. When you have a survival benefit, there is a PFS benefit. It would be unusual. And here again, a very robust difference in medium pfs about 17 months versus nine. Very remarkable data. Once again, there is no subgroup that pulled the results either in a negative or positive fashion. Everything lines up quite nicely. So in terms of safety and there was thankfully a very clear look at pneumonitis occurring. There is, there's been so many concerns about uh radiation postradiation with checkpoint inhibitors. And we saw earlier today that checkpoint inhibitors probably can be given safely concurrent with radiation, let alone afterwards. So the uh there are, as you might expect in a versus a placebo arm, there's going to be more S AES but they're not of a, a very high nature and percent. And, and so this appears quite modest and actually quite what we see in the absence of radiation. In other words, when we give checkpoint inhibitors in the adjuvant setting, post surgery, yes, add some toxicity but fairly minimal in comparing uh and looking at the robust efficacy outcomes. Uh they really don't uh challenge that expected S AES. This is nothing new what we've seen now for seven years since the first FDA approval of checkpoint inhibitors, not a unusual spectrum. They did look closely at the pneumonitis. That was the big fear. And yes, there's uh a slightly more with uh their V man but not a huge toxicity profile. And this was the conclusions of the trial which are self evident from the data. Very powerful survival PFS data. Absolutely can't be challenged. And so this really is uh now a standard of care. Thank you. Created by Related Presenters Joseph Treat, MD Professor, Department of Hematology/Oncology,Vice Chair, Education,Medical Director, Ambulatory Care,Fox Chase Cancer Center View full profile
