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Surgery and 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: Tuesday, Jan 22, 2019



Transcript:

H. Jack West, MD:
Let’s turn to the potential role for surgery, which certainly has a place, at least at some institutions, but it’s debatable about how appropriate surgery is for which subgroup of patients with stage III disease. This trial, PACIFIC, was for patients who were considered unresectable, but that isn’t really a well-defined entity, and I think it depends largely on the surgeon and certainly on the appearance of the scans and the patient. So do the PACIFIC trial and these more favorable results tip the scale, or do you think that surgery has the same role it always did? And what, if any, is the role for immunotherapy in surgical stage IIIa disease? Hoss, I’ll start with you.

Hossein Borghaei, DO: I think this is again, as was brought up by Charu earlier,…why you need a multidisciplinary team discussing these patients, looking at the pictures, looking at everything that you have and deciding how to do it. As far as I’m concerned, you decide whether a patient is a surgical candidate or not the day you see the patient in the clinic, seen by all disciplines, and the surgeon says this is a resectable disease, and the patient has the heart and the lung function and everything else to be a resectable patient.

Therefore, I’d like to make that decision as much as possible up front. We don’t live in a perfect world, and I realize that sometimes things change. But, to me, a resectable patient is decided right off the bat, right? I don’t like this wishy-washiness of “Oh, let’s do this. We can take a look.” I think those days are gone. We decide whether somebody is a surgical candidate or not, and we go based on that. I don’t think we should abandon surgery. I think there’s definitely a patient population with locally advanced disease who would benefit from the triplet therapy of chemo-RT [radiotherapy] followed by surgery. So I don’t think we should throw away the surgery for that patient population.

And, as far as I know, there really isn’t any kind of study to say if I-O [immuno-oncology] post chemo-RT and radiation is an effective treatment or not. And because these drugs have real toxicities, both financially and in terms of pneumonitis, colitis, all the other stuff that we know about, for a patient who’s gone through surgery, my practice is not to offer I-O immediately after that. My practice is to just enter the follow up period the way we’ve been doing it. But I’m not ready to do away with surgery, and I’m not offering I-O postsurgical resection for locally advanced disease.

Charu Aggarwal, MD, MPH: Same, although I feel that this whole tension that you see tested in our tumor boards about, “Oh my God, this patient is so close to being resectable, let’s take him to the OR [operation room],”…We used to actually not feel comfortable with taking the patient to the OR, based on the size of the lymph nodes or the location of the lymph nodes. I think that has decreased for the better. I think we didn’t used to do any favors to anyone by trying to take these borderline resectable patients to the OR. Their outcomes were not any better, even if their plan had been established in a multidisciplinary setting at the get go. The PACIFIC data have made the conversation a little more comfortable for everyone involved, where everyone says, “They’re not resectable—let’s take them to chemoradiation, let’s give them immunotherapy.” So I think it’s made it much more comfortable, especially with the overall survival data looking as positive as they do.

H. Jack West, MD: Yeah, and I agree that if nothing else,…chemoradiation and not going to the OR is not seen as the consolation prize that it was previously. There’s plenty to feel positive about. What about for neoadjuvant? We saw some very limited data about neoadjuvant nivolumab—a New England Journal of Medicine paper by Ford and colleagues—but that was 20 evaluable patients. It looks provocative, but obviously that’s not definitive. Does neoadjuvant have any role outside of a trial at this point?

Hossein Borghaei, DO: Neoadjuvant I-O, or just neoadjuvant in general?

H. Jack West, MD: No, I’m sorry. Let me say neoadjuvant immunotherapy.

Hossein Borghaei, DO: Right.

Charu Aggarwal, MD, MPH: Not at this time. Again, very provocative data. I think we have so much to learn in that setting. I love neoadjuvant studies because that’s a setting where you’re guaranteed paired biopsies or paired tumor samples. And there’s just so much to learn that can expand our understanding of how these drugs work and what we can do to improve our response. But clinically, I’m just not convinced that I would want to use it just yet.\

Hossein Borghaei, DO: I wouldn’t do it outside of a trial, but now we have intriguing data that have been published, as you suggested, by Ford and colleagues, and we saw a couple of other abstracts presented at World Lung in Canada just recently that, again, the data seem to be good. The data sets are small. These have to be replicated in a randomized study, but I think we might be looking at a new standard of care by the time these studies are done—at least that’s what the preliminary data seem to suggest. But we’ll see. But I agree that I wouldn’t do it outside of a clinical trial.

Transcript edited for clarity.

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Transcript:

H. Jack West, MD:
Let’s turn to the potential role for surgery, which certainly has a place, at least at some institutions, but it’s debatable about how appropriate surgery is for which subgroup of patients with stage III disease. This trial, PACIFIC, was for patients who were considered unresectable, but that isn’t really a well-defined entity, and I think it depends largely on the surgeon and certainly on the appearance of the scans and the patient. So do the PACIFIC trial and these more favorable results tip the scale, or do you think that surgery has the same role it always did? And what, if any, is the role for immunotherapy in surgical stage IIIa disease? Hoss, I’ll start with you.

Hossein Borghaei, DO: I think this is again, as was brought up by Charu earlier,…why you need a multidisciplinary team discussing these patients, looking at the pictures, looking at everything that you have and deciding how to do it. As far as I’m concerned, you decide whether a patient is a surgical candidate or not the day you see the patient in the clinic, seen by all disciplines, and the surgeon says this is a resectable disease, and the patient has the heart and the lung function and everything else to be a resectable patient.

Therefore, I’d like to make that decision as much as possible up front. We don’t live in a perfect world, and I realize that sometimes things change. But, to me, a resectable patient is decided right off the bat, right? I don’t like this wishy-washiness of “Oh, let’s do this. We can take a look.” I think those days are gone. We decide whether somebody is a surgical candidate or not, and we go based on that. I don’t think we should abandon surgery. I think there’s definitely a patient population with locally advanced disease who would benefit from the triplet therapy of chemo-RT [radiotherapy] followed by surgery. So I don’t think we should throw away the surgery for that patient population.

And, as far as I know, there really isn’t any kind of study to say if I-O [immuno-oncology] post chemo-RT and radiation is an effective treatment or not. And because these drugs have real toxicities, both financially and in terms of pneumonitis, colitis, all the other stuff that we know about, for a patient who’s gone through surgery, my practice is not to offer I-O immediately after that. My practice is to just enter the follow up period the way we’ve been doing it. But I’m not ready to do away with surgery, and I’m not offering I-O postsurgical resection for locally advanced disease.

Charu Aggarwal, MD, MPH: Same, although I feel that this whole tension that you see tested in our tumor boards about, “Oh my God, this patient is so close to being resectable, let’s take him to the OR [operation room],”…We used to actually not feel comfortable with taking the patient to the OR, based on the size of the lymph nodes or the location of the lymph nodes. I think that has decreased for the better. I think we didn’t used to do any favors to anyone by trying to take these borderline resectable patients to the OR. Their outcomes were not any better, even if their plan had been established in a multidisciplinary setting at the get go. The PACIFIC data have made the conversation a little more comfortable for everyone involved, where everyone says, “They’re not resectable—let’s take them to chemoradiation, let’s give them immunotherapy.” So I think it’s made it much more comfortable, especially with the overall survival data looking as positive as they do.

H. Jack West, MD: Yeah, and I agree that if nothing else,…chemoradiation and not going to the OR is not seen as the consolation prize that it was previously. There’s plenty to feel positive about. What about for neoadjuvant? We saw some very limited data about neoadjuvant nivolumab—a New England Journal of Medicine paper by Ford and colleagues—but that was 20 evaluable patients. It looks provocative, but obviously that’s not definitive. Does neoadjuvant have any role outside of a trial at this point?

Hossein Borghaei, DO: Neoadjuvant I-O, or just neoadjuvant in general?

H. Jack West, MD: No, I’m sorry. Let me say neoadjuvant immunotherapy.

Hossein Borghaei, DO: Right.

Charu Aggarwal, MD, MPH: Not at this time. Again, very provocative data. I think we have so much to learn in that setting. I love neoadjuvant studies because that’s a setting where you’re guaranteed paired biopsies or paired tumor samples. And there’s just so much to learn that can expand our understanding of how these drugs work and what we can do to improve our response. But clinically, I’m just not convinced that I would want to use it just yet.\

Hossein Borghaei, DO: I wouldn’t do it outside of a trial, but now we have intriguing data that have been published, as you suggested, by Ford and colleagues, and we saw a couple of other abstracts presented at World Lung in Canada just recently that, again, the data seem to be good. The data sets are small. These have to be replicated in a randomized study, but I think we might be looking at a new standard of care by the time these studies are done—at least that’s what the preliminary data seem to suggest. But we’ll see. But I agree that I wouldn’t do it outside of a clinical trial.

Transcript edited for clarity.
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