This video features Joseph Treat, MD presenting on Neoadjuvant Chemo-IO. This presentation was given at our October 20th Management of Early Stage Non-Small Cell Lung Cancer event in 2022.
Events in my career, which is the neo adjuvant treatment with lung cancer. So I'm gonna show you some data in this brief presentation and I would suggest that this is going to change the standard of care. We may not quite be there at the moment because there's still a lot of questions that remain. But I think this is really an important data set and like important trials in general. Many times they raise questions as much as they answer. So I'm gonna first talk about the endpoint that was used in the neo a german trial, chemo immunotherapy, which is the majority of what I'm going to talk about. The end points different than what we expect in lung cancer. What we've seen, it's using pathological complete response rate. Now, this is not a new concept. This has been kicked around at cooperative group trial levels for two decades. But and and that's good because there is a core of data which I think validates the impressive results of the trial. Then we're gonna go over in a few minutes so you can find any number of these data sets are typically small reportings, they all kind of saying the same thing if I could advance the slide uh in general, they use some version of chemo radiation or chemotherapy alone. And the important pieces here are really to look at that when patients achieve a pathological cr. Now that that also requires a definition. Some series just talk about the tumor itself, some and exclude or don't care if the lymph nodes are clear. And I think a true pathological pcR involves both the primary And the lymph nodes and what this data set shows from this particular reporting is a very long. Look at the last line there. The estimated five year long term survival in patients that got PCR is about it's 57%. It's outrageous expect half that number in in typical reportings that don't have PCR. And this again is a concept that is not new to long. In fact long is late to the game. This is something that has achieved FDA approval in the settings of breast cancer using PcR as the end point. So I'm making a suggestion that this is a very valid endpoint to use even though it's rather new in terms of lung reporting this paper nicely collated a bunch of things and if you look at the P. C. R. Five year survival it's the farthest column that is just astounding. So when a patient achieves a PCR with some type of induction therapy before surgery, it is a significant biological event another. And this is the most recent and reporting this is from the french concern. National system of trial testing. They have and it looked at chemo alone. So this is the most relevant data set in terms of a background for checkmate 0. 16 which we're going to look at in a second And look at the results in the first line they had about 8%. Now this is Chemo alone. Chemo alone followed by surgery, 8% PCR rate. And that's very consistent with older reportings that are around 6% pre pet days. So the pet introduction pet scans probably threw out some bad actors and you end up with 8% 8%. Keep that in mind. And again, the top line there is that if you achieve the PCR those survival rates are phenomenal talking 80%. An unbelievable figure. So this is the trial that was the new England Journal a few months ago from Patrick Ford at Hopkins. This is a follow up to his face to work with the same subject and this is neo achievement checkpoint inhibitor Nivaldo mob with chemotherapy. So a triplet as a preoperative maneuver. No radiation. And this is this is a landmark trial chief FDA approval a few months just a few months ago. So what was this? And this is worth going through a little bit of detail. This was obviously a phase three level trial. Chemo immuno versus chemo alone. Pre operatively in stages one B 23 A and reading the top lines there you can see the event free survival was much better in the triplet. The chemo. And you know, versus the chemo alone And the towards the middle of this paragraph from the results section, pathological complete response rate. This is the important number was 24%,, 24%. Now in the chemo immuno arm and the chemo alone arm. It was only 2%. I suggest that 2% is a lowball number that's not typically what you see in reporting the chemo alone should be about 678% not 2%. But it doesn't matter. Yes. The control arm, if you will underperformed it doesn't matter because the hypothesis arm with the immunotherapy and the chemo did so much better. Okay. And that has been a criticism that the control arm performed poorly. I think the correct answer is so what it is worth looking at demographics because they do tell you things mundane data can be very suggestive of questions or problems within a trial And I will draw your eye to the representation of Asian patients approximately 50%. That's a big number and it should have been accompanied by E. G. F. R. Reporting because right now we don't have an FDA approval of chemo in you know in an E. G. F. Our population and you can argue both ways. This may have swayed things better or worse but we don't know and that is a problem and I do know we're going to see this data later but we don't have it at the time of this reporting. We know half the population was asian we would expect as much as 35% of that 50% is E G. F are positive. Each fr rates in Asia 35 40% as opposed to 10%. In Caucasian populations. Draw a ride to the screen on screen And a quick disclaimer histology makes no impact on whether a patient she's PCR and so why is the 50% 50%? That's not what you might expect in a metastatic setting would be overwhelmingly uh not it would not be squamous. That's because in early stage disease there's a more equal distribution that's based on metastases potential. So this actually this number is actually correct. Should be about half and half screen on screen. Made no difference. The PTL status is very important and you'll see in the results it is very important. And as you might kind of project, the higher the PTL, the more benefit there was from the addition of the checkpoint hither this is uh excuse me, just meeting event free survival. And as you can see in in the forest plots in every subgroup there's benefit. It's it's an incredibly tight uniform result. It's not explained by one particular subset. Pulling the data not it's uniform. It's very reassuring that the data is probably very valid. This is who PCR 24% vs 2%. 24%. Amazing number. And as you can see it's it's across all subgroups less. So in the less than 1% PDF one though this is survival data hasn't been reached. Its that good whenever you see not reach. That's a good thing because the data is going to be better as it as it matures. Mhm. Be very quick about this. There were there really were no problems. In other words, there weren't a lot of S. A. S. Leading to patients being discontinued or they couldn't go to the O. R. Very low in between the two arms. Whether they had the M you know or not, there really was no difference in toxicity or discontinuation. That's important. There's some other points. Uh surgical cancelation rate actually favored the triple in arm with the immunotherapy. In other words, there was less disease progression was less in the triplet are serious adverse events really the same. And the clearance of a circulating tumor DNA was better in the triplet. You can't expect that. So where does this leave us? Well, it leaves us with some issues. It's a real positive trial. And if you're that 24% that achieves a PCR I don't think there's anything more to say but 76%, the vast majority do not. And what do you do? You did more chemo? Well, they already had three cycles. Do you want to give them more immuno while they've had three months worth? How can you improve on those numbers? And those will be the subject of cooperative group trials are being planned now. And cooperative group trials really give you sort of groupthink where the long docks really coalesce and think this is the direction we're headed in and what you're gonna see in the near future or trials that build on this and add some after surgical treatment and all the sub categories that have to be sorted out. Mr PDF one status mutation status that might influence response to immunotherapy. But this trial will be foundational and things will be added to it. So this is why I think something we have to really think about and begin to figure out how we're going to incorporate it in our practices. That's it. That was great, joe. Thanks so much.
