Management of Advanced NSCLC - Episode 5

Case 1: I-O Therapy & Autoimmune Conditions in NSCLC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDBenjamin P. Levy, MD:In the last few minutes, let’s talk about the fact that this patient has a preexisting autoimmune disorder—lupus.

Anne S. Tsao, MD:This is a tough one.

Benjamin P. Levy, MD:Yes, but the patient is well controlled, and is not on any medicine. From the data that we presented, and this paper that has come out at both of your institutions, we have seen a retrospective analysis looking at checkpoint inhibitors. This was 56 patients with a flare rate of 20%. Are you comfortable treating this patient who has well-controlled lupus with immunotherapy, given that we have nothing post-consolidation, for consolidation outside of immunotherapy for these patients?

Anne S. Tsao, MD:I probably would, just because, so far, the PFS [progression-free survival] benefit from the PACIFIC trial was so high. I would be willing to take the chance after going through the risks in great detail with the patient. And, I’d watch his renal function.

Paul K. Paik, MD:Yes. TheJournal of Clinical Oncologypaper was good to add to the body of literature. I think it’s problematic insofar that most of these patients still had relatively not terribly severe autoimmune diseases like rheumatoid arthritis, for example, right?

Benjamin P. Levy, MD:That’s right, yes.

Paul K. Paik, MD:There was a smattering who had things like ulcerative colitis, but the spectrum of autoimmune diseases was tilted toward things that are not as clinically severe when they flare, in particular. I think that limits our ability to figure out what to do when you have a patient with ulcerative colitis, Crohn’s disease, or even lupus. A lot of anecdotal experience will come into play with this. We were talking about this earlier, but I had a patient who had discoid lupus—cutaneous manifestation 15 years before. It went away very quickly. She was seen by a rheumatologist very frequently. And so, we had a discussion with the rheumatologist about the availability of immunotherapy. This was a stage IV patient, so her case was not exactly like this case. Her PD-L1 [programmed-cell death ligand 1] was high—80%. And so, pembrolizumab would be a standard for her. The rheumatologist did a panel of serologic tests. Nothing came back positive. The patient was doing great. We gave her pembrolizumab and she got lupus in a bad way, with a lot of dyspnea, arthralgia, and fatigue. That quickly went down with steroids. We thought, “OK, let’s try 1 more time,” because it went away very quickly. Well, it was worse the second time. Clearly, the immunotherapy uncovered this process, which was dormant. And so, I think it really requires a risk-benefit discussion with the patient. I think it begins and ends with that, really.

Benjamin P. Levy, MD:Would you have a risk-benefit discussion with this patient with lupus about the role of chemotherapy?

Paul K. Paik, MD:Yes, I would. It’s hard. Part of the difficulty with the PACIFIC trial is that for those patients who recur, the standard has already shifted during the lifetime of this trial, in terms of what we’ll talk about later—KEYNOTE-189 and KEYNOTE-407. Exactly what is the interplay with the OS [overall survival] advantage, in particular? That is really the key piece of data in the context of newer, better options. Are there better first-line therapies for patients with recurrent disease? Do you need to be so concerned about giving them some consolidative therapy in the IIIB setting, when you have something in the first-line metastatic setting that might work very well for them? These are things that come into play in that discussion.

Benjamin P. Levy, MD:Are there any other considerations? I think this was an excellent discussion, about the case. Really, the case highlights some of the challenges that we face in the clinic every day. Let’s move on to case 2, which Paul will be presenting.

Transcript edited for clarity.