Chapters Transcript Video Metastatic Disease: Consolidative Radiation Therapy Hi, everyone. You already know who I am. Uh, now we'll be talking about consolidated radiation, uh, like Haas said. Um, I'm really gonna be, sorry, no financial disclosures still, that didn't change. Um, Outlined. So I'm gonna talk about it in the targetable mutation negative population and then then in the targetable mutation positive population. I'm really gonna be focusing on the former rather than the latter. And this is, uh, just kind of a review of the data over time. Um, so there was a lot of, a lot of interest in local consolidation, um, early on. This is the Gomez study. It was one of the earlier studies. There were a few phase two studies that. Um, pretty, uh, pretty much all showed positive results. So this was a multi, uh, center randomized phase two study with, uh, 74 patients with stage 4 disease, with 3 or fewer metastases and no progression after 3 or greater months. And I actually feel like that point is important. Um, after frontline systemic therapy, um, and they were randomized to just maintenance therapy or consolidated radiation. And as you can see, the blue line is local, uh, consolidated therapy. Uh, those patients did better in terms of both OS and PFS. Uh, median OS, uh, was 17 months in the control arm and 41.2 months in the experimental arm and median PFS was 4.4 months in the control arm and 42 months in the experimental arm. So, pretty impressive results. Um, another A study that followed this is Saber Comet. I honestly feel like people know this study more because of its name. It's just a nice name. Uh. So it, it had all different tumor types. Um, in this case, the SAR or SBRT arm is in red. Um, and, uh, on the study, uh, it did have all different tumor types. Um, 18 of these patients were lung cancer patients. Um, and again, it showed a benefit in terms of 5-year OS and 5-year PFS. And this inspired, uh, guidelines. So this is the Astro Estro guidelines, which encourages, uh, for well-selected patients, uh, at least a conversation to discuss local consolidative therapy. Um, and this has also made its way into the NCCN guidelines. And so this is, I, I know I probably should have included the page before this, but this is along the oligometastatic track. And so it recommends if, uh, therapy is possible to go ahead and, um, treat with systemic therapy or just do definitive therapy, then restage, um, and then if you can, uh, definitively treat the metastatic sites, go ahead and do so. But a wrinkle in all of this. NRGLU 002, which is why this is now controversial. It was the largest phase 2 to 3 study, uh, to show the benefit of local consolidative therapy to a liga metastatic disease for non-small cell lung cancer patients. Um, so, and this is driver negative. So, um, patients with a liga metastatic disease who completed 4+ cycles of first-line therapy without progression. And 0 to 3 metastatic sites, and you might say, why 0? Because it doesn't include the primary. You could still have the primary. Uh, they were randomized 2 to 1. To local consolidative therapy, which was SBRT or surgery, uh, plus maintenance or maintenance alone. And it had 216 patients when it closed, and it closed at the completion of the phase two, portion because it did not meet a pre-specified endpoint. As you can see, the curves overlap. So 1 year and 2-year PFS and OS were not significantly different. And in fact, there was more toxicity in the local consolidated therapy arm, uh, rather than the maintenance arm. Oops, sorry. So really, you know, what happened here and, and obviously, all the results from the study are not out. I do think this is one of the problems of too many cooks in the kitchen. Maybe, um, one issue is this, you know, this study was done in the era of immunotherapy and some of the other studies weren't, but despite that, I think there was also a selection issue. And so, Uh, there was a very fuzzy definition of what constitutes a site. So patients could have multiple METs. Um, for example, we enrolled a patient at Fox Chase. She had numerable brain mets. They were treated prior to randomization, which were allowed, which was allowed. She still had her primary, she had nodal disease. She had 3 liver mets and an adrenal met, and she enrolled on this study as eligible. And so, Uh, there were, uh, quite a few patients that really we would not consider to be eligometastatic in the standard sense, which were eligible and enrolled onto this study. Um, it didn't require a response to treatments. As you can see, the majority of these patients had stable disease, but there was no waiting period. There was no time to declare itself. They went immediately on to local consolidative therapy. So you don't actually know. How responsive they actually were. And as I mentioned earlier, you could have any number of brain mets, but as long as they were treated prior to enrollment, you could still enroll onto the study as aligo metastatic. And then we have no data on the performance status of these patients per eligibility. Um, PS2 was allowed, but we don't know, you know, where those patients ended up or how they did. And so, I think it didn't give a good, Answer to whether we should treat a legome metastatic disease or not. I think, you know, most people in this room, if you had a patient with, you know, a single site of metastatic disease, would most likely send them for local consolidative therapy. Um, so I, I don't know how useful the study ended up being because I think that along the way, too many things got added into the protocol, too many patients became eligible, that really should not have been eligible in the first place. So now I'll talk about just really briefly about targetable mutations. Um, I just have two studies. Uh, typically, the, the mutation-positive patients, it's more, it's less of a question. It's more acceptable to treat oligometastatic disease, but I just have two studies. Um, so the CINDS trial is a randomized phase two trial comparing first-gen TKI versus first-gen TKI plus SBRT. In patients with 5 or fewer eggliga metastatic lesions without brain mets. Um, 133 patients were on this trial, and both median PFS and OS was superior in the SBRT arm. And it ended up being a pretty safe regimen. Uh, no grade 4 to 5 events, but there was 6% grade 3 to 4 pneumonitis in the SBRT arm. And then this is, uh, for thoracic consolidation and oligometastatic EGFR patients. It's a randomized phase 3 trial, um, with 118 patients. Um, median PFS was superior in the patients that got thoracic radiation. Median OS was also superior. Um, and there was better local control in the radiation arm, but there was more toxicity. So what are my conclusions, uh, early data did support the use of local consolidative therapy, but I, I really think it's a selection issue. You need to have very, very narrow selection criteria. You want them to have, you want your patients to have a response to systemic therapy or at least stand the test of time, because I think in that way, like if they have a response, you're saying, OK, I can see what it's doing to the macroscopic disease, and that's possibly what it's doing to the microscopic disease as well. Um, I, I don't think you should, you know, go crazy and, you know, treat multiple sites, especially multiple large sites. You know, probably the patients that do the best are the ones with 1 to 2 sites. Um, the ones with good performance status are the ones that do better. Um, and then, of course, the patients with the targetable mutations tend to be better. And then there are still many studies exploring this. And that's it. Created by Related Presenters Sameera Kumar, MD Department of Radiation Oncology Assistant Professor, Department of Radiation Oncology,Fox Chase Cancer Center View full profile
