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Durvalumab After CRT in Locally Advanced NSCLC

Panelists: Charu Aggarwal, MD, MPH, Hospital of the University of Pennsylvania; Hossein Borghaei, DO, Fox Chase Cancer Center; H. Jack West, MD, Swedish Cancer Institute
Published: Monday, Jan 14, 2019



Transcript:

H. Jack West, MD: Now, let’s turn back, though, to the issue. You said that about a quarter, even a little more than that had gotten induction. I personally would not be a fan of intercalating consolidation chemotherapy before the durvalumab. That’s not how the trial was done, and it’s not like there’s a scintilla of evidence to support it. Induction was used, and I’ve talked with Mark Socinski, MD, who’s done a lot of work in this, and has raised the point that there are some potential advantages of induction, one being that you can get systemic therapy started at a systemic dose. Sometimes it takes a few weeks to get the chemotherapy and radiation coordinated, and you can get a foot in the door while the SIM [simulation] is going on and without losing ground.

For some of my patients who I may have some reservations about their ability to do concurrent, we can make sure they’re doing OK with the initial systemic portion. It was part of the trial. It was totally feasible. And, even though the CALGB trial going back a little over a decade was not positive, it did show a 2 month difference in median overall survival. It was not the most negative trial. I think it had some methodological issues…. It’s hard for me to say that it would be an outlandish idea, and I think it is an option. Charu, your thoughts on induction? Do you do that for some of your patients?

Charu Aggarwal, MD, MPH: So I do it for some patients, I think again going back to the other point that these patients should be discussed in a multidisciplinary setting. And if there is something that’s already telling me that I need to consider induction chemotherapy, maybe their burden of disease is a little larger than we would feel comfortable with, encompassing in a radiation field or maybe they’re borderline performance status and I want to be able to just give them chemotherapy before I take them to combination chemoradiation. I think the decision should be made up front. I would hate for a patient to settle for a sequential approach when our intent was to do chemotherapy and radiation concurrently. So I think as long as it’s discussed up front with the patient that I’m going to watch you very closely but my intent is still to take you to chemoradiation, I think that’s a very fair strategy to do that and I think totally in line with what was done on the trial, to still come back with durvalumab.

Going back to the timing issue of how and when to start durvalumab, I would just add that I agree with you that maybe those patients that were going to do better anyway, because they were either better performers, low burden of disease, younger, healthier, fitter. But I think as medical oncologists we should also be able to prevent delays, and I feel that sometimes the chemotherapies that we may administer may delay things. I think cisplatin/etoposide can delay my administration of durvalumab, even if I didn’t want it. And I feel like carboplatin and paclitaxel may make it easier because I’m monitoring their counts every week, I’m seeing them every week, I have the ability to hold chemotherapy or delay it or defer it. And I feel like that’s probably the most controlled environment I have as a medical oncologist. That’s just how I feel.

Hossein Borghaei, DO: I agree with you. I think again that’s one of the reasons I don’t want to do a lot of consolidation chemotherapy right after chemo-RT [chemoradiation therapy] because you could delay initiation of immunotherapy which I think is the key here. So I’m not really in favor of doing consolidation chemotherapy after chemo-RT. And that point I absolutely agree with you. I think going back to the induction, I’ve never done it in our institution. That’s not standard of care. We sort of interpret the CALGB study as being basically a negative trial. I see Mark’s point. I’ve had discussions with him also, and I agree that he does raise a couple of good points. My biggest question is do you need it? And that I don’t have an answer to because we really didn’t design a trial to look at those specific kinds of questions.

And I think, again, you’re coming out and making a recommendation about how to treat the patient. When you don’t have the data it’s kind of hard. Yes, you can do it. Yes, it was done on the study. Obviously it wasn’t detrimental, although we don’t have the details of those 28% who got the induction and what happened to them. I don’t see anything wrong with them, I would just argue that the data are not very strong in support of doing induction. But patients like you mentioned, if they have a lot of disease burden, I’ve never been a big fan or a believer in down staging, so to speak, with chemotherapy because you use CARBO/Taxol [carboplatin/paclitaxel] a lot in the metastatic setting. How often do you see that wonderful of a response? Yeah, occasionally it can happen, but this concept of down staging and making it a little bit smaller, I never bought into that, honestly. So we haven’t or I haven’t tried that, and I know a lot of my colleagues, at least at Fox Chase, don’t really do a lot of induction up front. But, again, because it was part of a study, I have no objections if somebody wants to try that.

Charu Aggarwal, MD, MPH: Yeah.

H. Jack West, MD: Well, I have had an occasional patient for the reasons I mentioned and also for the question of, yeah, you could do it with the radiation field that’s there. But it wouldn’t bother me at all if it shrank and there was a smaller radiation field. In fact, the last person I’ve done this for, that’s what happened, and great.

Let’s turn to the timing of the durvalumab. In the study, patients would get imaging after chemoradiation. If they had not had progression, or toxicity issues, or a drop in their performance status, they would go on to the durvalumab. My standard timing for doing the post-chemoradiation imaging was about 3 or 4 weeks after, so that we could see the extent of the radiation effect which often extends beyond a week or 2. I have tended to shift that a little earlier, just trying to get the durvalumab started a little earlier, not that I think it’s critical but just because there seems to be a little more of a gravitational pull toward if you can get it done quickly in the wake of chemoradiation, maybe that is a good thing. Have you changed the timing of your imaging, and what’s your goal for starting durvalumab? Would you want to start it a week later? Would you feel no issues at all if it’s 5 or 6 weeks?

Charu Aggarwal, MD, MPH: I completely agree with you that it used to be 3 to 4 weeks in the days when I was using consolidation CARBO and paclitaxel. I used to have patients come back at about 3 to 4 weeks, get a scan, they looked good, they’ve recovered. Okay, now you can start your consolidation. I have started moving that up a little bit. I am getting restaging scans at about 2 weeks. I feel that 1 week is probably still too early. I think patients are just sick of coming every day by that time, and they just want a couple of weeks to relax and not see us, which is fine. I don’t take it personally.

H. Jack West, MD: My patients love seeing me, so it’s a little different.

Charu Aggarwal, MD, MPH: I don’t take it personally.

H. Jack West, MD: No. Go ahead.

Charu Aggarwal, MD, MPH: I think 2 weeks is probably my goal and I’m trying to meet that.

H. Jack West, MD: Hoss?

Hossein Borghaei, DO: Let’s just remind everybody that our radiation oncology colleagues don’t like a CAT [computed axial tomography] scan that soon, right? But we’re doing the scan to make sure there’s no evidence of metastasis, really. We’re not looking for a response, and I do mine in 2 weeks also to start DURVA [durvalumab]. So that’s been my practice.

H. Jack West, MD: And I’m thinking the same thing. Back when this was the only thing that we were relying on and there was nothing necessarily to follow it, it mattered more to us than now, the hurdle being no progression, good enough, let’s keep going. And then we get to take credit if it’s continuing to shrink, so much the better.

Hossein Borghaei, DO: Yeah.

Transcript Edited for Clarity

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Transcript:

H. Jack West, MD: Now, let’s turn back, though, to the issue. You said that about a quarter, even a little more than that had gotten induction. I personally would not be a fan of intercalating consolidation chemotherapy before the durvalumab. That’s not how the trial was done, and it’s not like there’s a scintilla of evidence to support it. Induction was used, and I’ve talked with Mark Socinski, MD, who’s done a lot of work in this, and has raised the point that there are some potential advantages of induction, one being that you can get systemic therapy started at a systemic dose. Sometimes it takes a few weeks to get the chemotherapy and radiation coordinated, and you can get a foot in the door while the SIM [simulation] is going on and without losing ground.

For some of my patients who I may have some reservations about their ability to do concurrent, we can make sure they’re doing OK with the initial systemic portion. It was part of the trial. It was totally feasible. And, even though the CALGB trial going back a little over a decade was not positive, it did show a 2 month difference in median overall survival. It was not the most negative trial. I think it had some methodological issues…. It’s hard for me to say that it would be an outlandish idea, and I think it is an option. Charu, your thoughts on induction? Do you do that for some of your patients?

Charu Aggarwal, MD, MPH: So I do it for some patients, I think again going back to the other point that these patients should be discussed in a multidisciplinary setting. And if there is something that’s already telling me that I need to consider induction chemotherapy, maybe their burden of disease is a little larger than we would feel comfortable with, encompassing in a radiation field or maybe they’re borderline performance status and I want to be able to just give them chemotherapy before I take them to combination chemoradiation. I think the decision should be made up front. I would hate for a patient to settle for a sequential approach when our intent was to do chemotherapy and radiation concurrently. So I think as long as it’s discussed up front with the patient that I’m going to watch you very closely but my intent is still to take you to chemoradiation, I think that’s a very fair strategy to do that and I think totally in line with what was done on the trial, to still come back with durvalumab.

Going back to the timing issue of how and when to start durvalumab, I would just add that I agree with you that maybe those patients that were going to do better anyway, because they were either better performers, low burden of disease, younger, healthier, fitter. But I think as medical oncologists we should also be able to prevent delays, and I feel that sometimes the chemotherapies that we may administer may delay things. I think cisplatin/etoposide can delay my administration of durvalumab, even if I didn’t want it. And I feel like carboplatin and paclitaxel may make it easier because I’m monitoring their counts every week, I’m seeing them every week, I have the ability to hold chemotherapy or delay it or defer it. And I feel like that’s probably the most controlled environment I have as a medical oncologist. That’s just how I feel.

Hossein Borghaei, DO: I agree with you. I think again that’s one of the reasons I don’t want to do a lot of consolidation chemotherapy right after chemo-RT [chemoradiation therapy] because you could delay initiation of immunotherapy which I think is the key here. So I’m not really in favor of doing consolidation chemotherapy after chemo-RT. And that point I absolutely agree with you. I think going back to the induction, I’ve never done it in our institution. That’s not standard of care. We sort of interpret the CALGB study as being basically a negative trial. I see Mark’s point. I’ve had discussions with him also, and I agree that he does raise a couple of good points. My biggest question is do you need it? And that I don’t have an answer to because we really didn’t design a trial to look at those specific kinds of questions.

And I think, again, you’re coming out and making a recommendation about how to treat the patient. When you don’t have the data it’s kind of hard. Yes, you can do it. Yes, it was done on the study. Obviously it wasn’t detrimental, although we don’t have the details of those 28% who got the induction and what happened to them. I don’t see anything wrong with them, I would just argue that the data are not very strong in support of doing induction. But patients like you mentioned, if they have a lot of disease burden, I’ve never been a big fan or a believer in down staging, so to speak, with chemotherapy because you use CARBO/Taxol [carboplatin/paclitaxel] a lot in the metastatic setting. How often do you see that wonderful of a response? Yeah, occasionally it can happen, but this concept of down staging and making it a little bit smaller, I never bought into that, honestly. So we haven’t or I haven’t tried that, and I know a lot of my colleagues, at least at Fox Chase, don’t really do a lot of induction up front. But, again, because it was part of a study, I have no objections if somebody wants to try that.

Charu Aggarwal, MD, MPH: Yeah.

H. Jack West, MD: Well, I have had an occasional patient for the reasons I mentioned and also for the question of, yeah, you could do it with the radiation field that’s there. But it wouldn’t bother me at all if it shrank and there was a smaller radiation field. In fact, the last person I’ve done this for, that’s what happened, and great.

Let’s turn to the timing of the durvalumab. In the study, patients would get imaging after chemoradiation. If they had not had progression, or toxicity issues, or a drop in their performance status, they would go on to the durvalumab. My standard timing for doing the post-chemoradiation imaging was about 3 or 4 weeks after, so that we could see the extent of the radiation effect which often extends beyond a week or 2. I have tended to shift that a little earlier, just trying to get the durvalumab started a little earlier, not that I think it’s critical but just because there seems to be a little more of a gravitational pull toward if you can get it done quickly in the wake of chemoradiation, maybe that is a good thing. Have you changed the timing of your imaging, and what’s your goal for starting durvalumab? Would you want to start it a week later? Would you feel no issues at all if it’s 5 or 6 weeks?

Charu Aggarwal, MD, MPH: I completely agree with you that it used to be 3 to 4 weeks in the days when I was using consolidation CARBO and paclitaxel. I used to have patients come back at about 3 to 4 weeks, get a scan, they looked good, they’ve recovered. Okay, now you can start your consolidation. I have started moving that up a little bit. I am getting restaging scans at about 2 weeks. I feel that 1 week is probably still too early. I think patients are just sick of coming every day by that time, and they just want a couple of weeks to relax and not see us, which is fine. I don’t take it personally.

H. Jack West, MD: My patients love seeing me, so it’s a little different.

Charu Aggarwal, MD, MPH: I don’t take it personally.

H. Jack West, MD: No. Go ahead.

Charu Aggarwal, MD, MPH: I think 2 weeks is probably my goal and I’m trying to meet that.

H. Jack West, MD: Hoss?

Hossein Borghaei, DO: Let’s just remind everybody that our radiation oncology colleagues don’t like a CAT [computed axial tomography] scan that soon, right? But we’re doing the scan to make sure there’s no evidence of metastasis, really. We’re not looking for a response, and I do mine in 2 weeks also to start DURVA [durvalumab]. So that’s been my practice.

H. Jack West, MD: And I’m thinking the same thing. Back when this was the only thing that we were relying on and there was nothing necessarily to follow it, it mattered more to us than now, the hurdle being no progression, good enough, let’s keep going. And then we get to take credit if it’s continuing to shrink, so much the better.

Hossein Borghaei, DO: Yeah.

Transcript Edited for Clarity
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