Chapters Transcript Video Locally Advanced Disease: New Paradigm - How to Move Forward Hi, everyone. My name is Doctor Samira Kumar. Um, I am a thoracic radiation oncologist at Fox Chase. Uh, the topic of my talk is a new paradigm, how to move forward in this setting. Uh, I took this to mean, well, you know, what are, what is the hot new things coming through in unresectable stage 3 non-small cell lung cancer. I, I don't have any disclosures. Um, so here's just a brief outline. I'm gonna be talking about some early phase, early data, um, that, that's kind of buzzing around and interesting. So first, I'll start with new applications of neoadjuvant therapy. Uh, I'll talk about the, uh, recently, um, presented results of MDT Bridge. Um, these are interim results. Um, I'll then Talk about theR study, which is a super cool, uh, small phase two study. Um, and then I'll talk about some trials that are still in process, including NRGLU 008, which brings SBRT to the unresectable stage three setting, as well as Pacific 8 and Pacific 9, which add agents to the consolidation to Valumab. So, I'll start with the MDT bridge study. This is a non-randomized phase two study, uh, and it enrolled patients with stage 2B to 3B, non-small cell lung cancer who were deemed to be resectable or borderline resectable by a multidisciplinary tumor board assessment. Um, these patients were then treated with 2 cycles of DERV plus chemo, and then reassessed. At reassessment, if they were deemed to be resectable, they went on to get more DEA plus chemo, and then surgery. However, if they were unresectable at this time, they got chemo radiation, and then everyone got 1 year of DEUA. And the primary endpoint was the resection rate, people who underwent definitive surgery. And as you can see, uh, they accrued resectable and borderline resectable patients, and the majority of these borderline resectable patients were deemed to be resectable upon their reassessment. And then out of those 76 patients who were deemed to be resectable, the vast majority, 72 of them ended up going to surgery. Um, and the minority of them ended up unresected. Oops. This is just, uh, tables with the same data, but the, the majority of people who were unresected did go on to get chemo radiation. However, 4 did not. Um, of the patients that were deemed to be unresect sorry, that were deemed to be resectable, that ended up not getting surgery. So the unresected, there were only 4 of those patients, but 3 of those 4 were, uh, in the borderline category to begin with. Um, so a total of, uh, 95% of people got surgery, um. Sorry, a total of 85% of all patients got surgery. Um, and of those 85% that got surgery, approximately 95% got an R0 resection. Uh, those deemed to be upfront resectable obviously did better. Approximately 93% of those patients ended up going to surgery, and 98% ended up getting an R0 resection. Uh, those that were deemed to be borderline resectable, um, 71% ended up going to surgery with an 85%, uh, rate of R 0 resection. And so this is just some interesting early data, you know, uh, how do we deal with these, uh, borderline resective. Patients, you know, these are patients that may have gone on to get chemo rads up front, but, uh, this is, this is still a very early phase two study, uh, but it could guide future research into what to do with this category in between. Um, they did not, uh, present what, you know, what they deemed to be, uh, borderline, uh, so I don't have that information. Um, then I want to talk about the InR study, which is a very interesting, uh, small randomized phase two study, uh, that dealt with unresectable stage 3 non-small cell, uh, lung cancer without a driver mutation, um, and no prior therapy. These patients were randomized 1 to 1 to chemo immuno for 2 cycles, which you can see on the top versus chemo alone. And then everyone got definitive concurrent chemo rads to 60 to 66 gray. If these patients did not have progression, they then went on to get more immunotherapy, and the primary endpoint was PFS. And as you can see, the patients in the chemo immuno arm did significantly better in terms of PFS. There is a caveat to this though. If you look at the median PFS for the chemo alone arm, it's 12.4 months, and this is below what we see in Pacific. So, that is something to keep in mind. Pacific was 16.9 months. And the objective response rate was also significantly better in the chemo IO arm versus chemo alone. And again, this is a single-center randomized phase two study, uh, with a few patients. And so it's, it's, it definitely needs, um, further investigation and larger trials. I'll then talk about some studies that are ongoing right now, which you may hear about in the future. Uh, this is NRGLU 008, which, as I mentioned earlier, is bringing SBRT to the unresectable, uh, stage 3 setting. Uh, so this is for locally advanced node positive, uh, stage 2 and 3 non-small cell lung cancer patients. Notice that it, it does not say without a driver mutation. Uh, they are randomized, uh, to receive, uh, standard of care, oops, which you can see on the bottom, chemo radiation. Uh, versus SBRT to the primary and chemo radiation to the mediastinum. Even though the schema says maintenance immunotherapy afterwards, um, these patients, for example, if they have an EGFR mutation, can get osamerinib instead. And so, this trial has accrued about 40% of its patients and is still ongoing. Um, and then the next two trials I'll talk about are Pacific 8 and Pacific 9. And these, uh, both of these, uh, trials are adding, um, agents to the consolidationdervalumab. So, uh, Pacific 8 is a, uh, phase 3 study in patients with unresectable stage 3 non-small cell lung cancer. Uh, they're randomized 1 to 1 to get standard of care, uh, chemo, or sorry, they get standard of care chemo rads prior to randomization, and then they go on to get, uh, durvalumab, which you can see down at the bottom, plus placebo, or, uh, durvalumab plus domvanilumab, which is an anti-digit drug, and this study is still accruing. Uh, Pacific Nine has completed accrual, I believe. Um, it's similar, uh, in that patients are randomized after they get concurrent chemo rides and have not had any progression. Um, it's a three-arm study. So the standard of care is down at the bottom with DEURVA. Um, and then the ARMA includes D DURV plus oleummab, which is a CD 73 inhibitor, and ARMB includes DURV plus monolizumab, which is an NKG2A inhibitor. Uh, so my conclusions are, there are some new applications to neoadjuvant chemo IO which are really exciting and promising. And then outside of neoadjuvant therapy, there are, you know, other trials that are ambitious and offering different RT techniques and additions to adjuvant therapy. 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
