Practice Changing Trials in Advanced Non-Small Cell Lung Cancer - Episode 3

Surgery in the Context of Immunotherapy for Locally Advanced NSCLC


Benjamin P. Levy, MD: So, I got a call from a patient the other day who was interested in coming to see me because she wanted a second opinion. And this is a patient who had single-station N2 disease, young patient, fit, PD-L1 100%. It brings into the fold, do we need to change our calculus on these patients with stage 3 disease who we’re pushing for surgery, which is still curative, given that we’ve got durvalumab? Or do we still need to think about every patient the same as we did before, that the patients who are eligible for surgery should go on to surgery even though we have this wonderful data with durvalumab?

Hossein Borghaei, DO, MS: I would not.

Suresh S. Ramalingam, MD: When you have something exciting like PACIFIC, you are naturally inclined to extend the benefits of the drug to other patient populations. But you have to remember that stage 3 is a very heterogeneous disease. This trial specifically selected patients with surgically unresectable disease. If you have a patient with surgically resectable disease, I think that’s a multidisciplinary decision as to whether that patient gets concurrent chemotherapy with radiation followed by surgery or chemotherapy followed by surgery. And some patients may get postoperative RT. But that’s not the setting where durvalumab has been studied, and we should wait for that. There are ongoing studies in stage 1B, 2, and 3A that are specifically looking at where immune checkpoint inhibition fits on. So, through the ALCHEMIST—ECOG-ACRIN is leading this trial—and other groups, including Alliance—which Tom leads—and SWOG and NRG, they are comparing nivolumab versus observation in surgically resectable patients. And those trials are quite far along, so we should have the data in the next couple of years, at least from some of these adjuvant studies. There’s also the neoadjuvant approach where you give, in the experimental setting, immune checkpoint inhibition, and we’ve seen some promising results. So, that’s also being studied in large randomized trials. So, the surgically resectable population is a different group.

Benjamin P. Levy, MD: Than the unresectable.

Suresh S. Ramalingam, MD: We should not mix the PACIFIC data with those patients.

Benjamin P. Levy, MD: Absolutely agree, yes.

Naiyer A. Rizvi, MD: I think that there are patients who are more borderline, maybe have multiple nodal stations or PFTs (pulmonary function tests) you’re not sure about, and I think that in the past, you would do everything possible to get those borderline patients to surgery. And now, I think you may not feel as much pressure and you may choose a chemoradiation route rather than do everything to get them to surgery.

Benjamin P. Levy, MD: A few practical considerations, clinical points as they relate to the PACIFIC trial. In the past, I was doing concurrent chemoradiation and getting a PET scan 3 months afterwards. Do we need to get a CT scan right away when we’re done, just to assure stable disease, so that patients can go on to durvalumab? Is that a message to clinicians to make sure there’s at least stable disease or do we just go ahead and start the durvalumab without any imaging?

Hossein Borghaei, DO, MS: Yes.

Benjamin P. Levy, MD: I think they had to have some sort of imaging post concurrent chemoradiation. If you’re going to start the durvalumab within 7 days, I think you have to have some sort of scan showing disease stability. Is that going to change the way it’s managed?

Naiyer A. Rizvi, MD: I think for me, we actually found that there was a significant improvement in response with the durvalumab versus placebo when you start.

Benjamin P. Levy, MD: Interestingly, the placebo response rate was 15%. I’m not sure how that happened.

Naiyer A. Rizvi, MD: Well, because there’s still some sequalae of the chemotherapy and RT that they received. To me, I typically would get just a non-contrast chest CT to get a new baseline image of their lungs, frankly, more than anything else. If they develop…

Roy S. Herbst, MD, PhD: Pneumonitis.

Naiyer A. Rizvi, MD: Yes, and obvious progression.

Thomas E. Stinchcombe, MD: That’s what I’ve done is just a scan. I monitor them every couple of months with a scan just to make sure they’re not progressing.

Hossein Borghaei, DO, MS: Right, but we have changed our practice a little bit in light of PACIFIC. Now we are doing it. I wasn’t doing a CT right after chemotherapy/RT, but now I am doing one for all of the reasons that was just mentioned, especially the pneumonitis part. You want to make sure there’s not a grade 1 pneumonitis, asymptomatic, but you can see radiographically just in case.

Benjamin P. Levy, MD: And one more practical consideration. For those patients who aren’t candidates for concurrent but need it sequentially, chemotherapy followed by radiation, can we apply the same data here? Would you be reluctant to use durvalumab in the setting of a sequential approach? Not many of my patients get sequential. We try for concurrent based on a survival improvement for concurrent versus sequential. But for a patient in whom you do have to give sequential, who’s unresectable, chemotherapy followed by radiation, would you consider durvalumab in that setting?

Hossein Borghaei, DO, MS: I would.

Suresh S. Ramalingam, MD: That’s a relatively small subset of patients, and you have to go back to why you did not do concurrent and why you went with sequential in that situation. That might bear into whether you actually won’t do anything, not just durvalumab in an aggressive manner or not. So, I would say the answer is that it depends on the patient.

Roy S. Herbst, MD, PhD: Right, on a case-by-case basis. There aren’t data in that setting, but I’d be very comfortable giving it. But, again, if there are performance status issues or other contraindications, of course, no.

Transcript Edited for Clarity