Implications for Using Durvalumab in Stage 3 NSCLC



Benjamin P. Levy, MD: In the theme of subgroup analysis, I have a couple of comments. One is, again, that the never-smoker group in this patient population benefited. The only group that really didn’t benefit was the one comprised of EGFR-mutant patients. This came up in the discussion. What do we do with those patients? I know it’s a small number. I think it was a total of 20 to 30 patients.

Corey J. Langer, MD, FACP: The confidence intervals overlap, but it was still in the right direction.

Benjamin P. Levy, MD: So, what do we do with an EGFR-mutant patient who has stage III disease? I would still consider giving these patients concurrent chemoradiation followed by durvalumab.

Corey J. Langer, MD, FACP: I would have equipoise for doing a trial in the mutant population, comparing durvalumab to a tyrosine kinase inhibitor. I don’t think we have data on your original trial, Karen, on the percentage of patients who had EGFR mutations and predated the mutation error…?

Karen Kelly, MD: We do not, and that’s unfortunate. It was really getting the samples and doing that. We just don’t have the samples to do that on. That’s unfortunate.

Mark A. Socinski, MD: But yes, there was a small representation of EGFR-mutant patients.

Karen Kelly, MD: Very small.

Mark A. Socinski, MD: It’s hard to know what to do with those patients.

Corey J. Langer, MD, FACP: It’s a dilemma that we have to grapple with.

Benjamin P. Levy, MD: It was the only group that didn’t benefit.

Karen Kelly, MD: Right. My personal preference would be to give them the chemoradiation therapy and not…

Corey J. Langer, MD, FACP: And not give them durvalumab?

Karen Kelly, MD: I would not in that tiny, tiny patient population.

Corey J. Langer, MD, FACP: I think I’m going to reserve judgment until we see the overall survival curves. I’m sure it has to be broken down to that group.

Karen Kelly, MD: It’s a very small group. We have other data to say that patients don’t do well with immuno-oncology therapy. In the stage 4 setting, we have consistently shown that they do not do well.

Mark A. Socinski, MD: At least with an immuno-oncology monotherapy.

Corey J. Langer, MD, FACP: And that’s compared with an active control.

Karen Kelly, MD: Yes, but this is monotherapy that we’re doing.

Benjamin P. Levy, MD: Postradiation.

Karen Kelly, MD: Yes, but still EGFR-positive.

Mark A. Socinski, MD: Were you surprised by the rates of pneumonitis being so low?

Karen Kelly, MD: I am not surprised by that. Again, we could split hairs a little bit, but pneumonitis is a little bit less in PD-L1 inhibitors than it is in PD-1 inhibitors.

Corey J. Langer, MD, FACP: I was surprised. I thought it would be higher. I think that the Hoosier group…looked at straight consolidation with pembrolizumab, and the rates were higher. They were acceptable, but they weren’t 2% or 3%. They were more on the order of 5% to 8%.

Benjamin P. Levy, MD: Wasn’t this initially supposed to be a Cooperative Group study? Weren’t there major concerns about the pneumonitis, the immunotherapy, after radiation, and it sort of put it dead in the water?

Karen Kelly, MD: I don’t know.

Mark A. Socinski, MD: I’m not sure about that. To get back to the 2-week subset analysis, the original design of the trial required patients to be randomized within 2 weeks.

Karen Kelly, MD: That’s true.

Mark A. Socinski, MD: There were accrual issues, and that’s why it went to 6 weeks. To Corey’s point, it does kind of lead to some decision making regarding the timing of radiation, of CT scanning, and that sort of thing. What do you do?

Corey J. Langer, MD, FACP: And also, would you offer this to a patient who has any degree of pneumonitis?

Mark A. Socinski, MD: Right.

Corey J. Langer, MD, FACP: Granted, you’re going to see radiation changes on imaging. That’s not pneumonitis. That’s not clinical or symptomatic…

Mark A. Socinski, MD: Right.

Corey J. Langer, MD, FACP: But for somebody who’s actually starting to get symptomatic, you’re initiating steroids, which we know may counteract. That’s the patient in whom I’ll probably let things quiet down. I may make the decision later. I may just give them a consolidated…

Karen Kelly, MD: Again, we don’t know much about this group of patients and what the radiation fields look like. There are a lot of unanswered questions.

Corey J. Langer, MD, FACP: I would love to see a breakdown for those who’ve had PET simulation.

Karen Kelly, MD: Looking at that and PET simulation, I think they probably have all of that data available.

Corey J. Langer, MD, FACP: I hope so.

Karen Kelly, MD: These are really important questions, particularly as we consider what comes next in this field. What comes next?

Corey J. Langer, MD, FACP: Next comes immuno-oncology combinations, I imagine.

Karen Kelly, MD: The 1 combination that is now not going forward was the IDO and durvalumab combination. That’s not going forward. What other maintenance combinations could you put in there? Anti-CTLA-4 would be put…

Mark A. Socinski, MD: Looking at it currently.

Karen Kelly, MD: And then, moving it concurrently. MD Anderson Cancer Center has completed a trial that they’ll present data on at the World Conference on Lung Cancer. They’ve looked at paclitaxel/carboplatin plus an immuno-oncology.

Corey J. Langer, MD, FACP: And radiation.

Karen Kelly, MD: And radiation.

Corey J. Langer, MD, FACP: Concurrently.

Karen Kelly, MD: It is feasible and promising, and, hopefully, we can move forward in a Cooperative Group situation. I think that would be what many investigators are going to be looking at. Plus, we now have a large body of evidence to say that chemotherapy plus immuno-oncology work well together and are tolerated in the stage 4 setting. And we know that radiation is also a very good immunomodulator. I think some of the questions may become: Do we need the paclitaxel/carboplatin at some point? What chemotherapy do you really need at that point down the road? Or, do you need paclitaxel and carboplatin?

Corey J. Langer, MD, FACP: I think I’d would want to ask the plus/minus radiotherapy question first.

Karen Kelly, MD: Sure.

Corey J. Langer, MD, FACP: That’s the easiest to do, and I think that’s an important one. I don’t think we’re doing well enough in this disease to dial back on the treatment. This is not HPV-positive oropharyngeal cancer, where we were overtreating patients. We may argue that we’re overtreating this and are causing toxicity. But until our outcomes start approaching 70% to 80% and 5 or 6 years of survival, I’m not ready to necessarily cut back.

Karen Kelly, MD: I think you have to remember that even though we may give a lot of paclitaxel and carboplatin, there are still a lot of people who are giving cisplatin/etoposide, which is toxic. And people are giving pembrolizumab/cisplatin, and pembrolizumab/carboplatin, and…

Corey J. Langer, MD, FACP: Well, cisplatin/etoposide often has less pneumonitis after…

Karen Kelly, MD: Yes, but it is toxic at the end. It is not easy. A lot of people still give that. Certainly, weekly paclitaxel/carboplatin. Having said that, again, every patient’s individualized. There are patients who can’t tolerate paclitaxel/carboplatin with radiation therapy. I just had a patient like this the other day. She was hospitalized twice. All of these are rare situations, but I think that was really a provocative question. Much more work does need to be done.

Transcript Edited for Clarity

Related Videos
Chul Kim, MD, MPH
Salman R. Punekar, MD, Mayo Clinic
Federico Cappuzzo, MD
Pasi A. Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology, director, Belfer Center for Applied Cancer Science, director, Chen-Huang Center for EGFR Mutant Lung Cancers, senior physician, David M. Livingston, MD, Chair, Dana-Farber Cancer Institute; professor, medicine, Harvard Medical School
Edgardo S. Santos Castillero, MD, FACP
Joshua K. Sabari, MD
Coral Olazagasti, MD
Samuel Rosner, MD