Toxicity Profiles of Immunotherapy Agents in Advanced NSCLC


A brief review of AEs seen with immunotherapy in advanced non–small cell lung cancer followed by advice on how to nuance safety data in this setting.


Stephen V. Liu, MD: Neal, before I move on to this next section, one thing I was wondering is, when we think of immunotherapy, we think of that long-term benefit, survival benefit, for some patients’ long-term survival. And for some patients, a treatment that really won’t stop working. That’s really what we hope for. But there’s always toxicity with everything that we do, [and] there are always risks with every treatment that we give. What are some of the common adverse events that occur while patients are receiving immunotherapy in your practice?

Neal Ready, MD, PhD: The immune-related toxicities with mono-immune therapy, many patients will have them, but often they’re grade 1 or grade 2. And those could be rashes, fatigue, some joint pain, [and] endocrine problems like developing hypothyroidism. About 10% will have clinically significant toxicities, such as immune pneumonitis, colitis, [and] immune hepatitis. Some of the toxicities that are grade 3 and grade 4 require us to hold therapy and treat with high-dose steroids. And then there are still 1% or 2% of patients who have severe, life-threatening immune toxicities, including pulmonary [and] GI [gastrointestinal]. Cardiac, fortunately, is rare. Central nervous system, that’s rare. But that we do have to keep [them] in mind because occasionally they happen and require specialized treatment in the hospital. But overall, compared [with] other treatment options, less toxic and capable of giving prolonged survival.

Stephen V. Liu, MD: These are great points. And we don’t want to avoid discussing toxicity. When we talk about [adverse] effects of immunotherapy, it’s not meant to discourage people from using it because, as you mentioned, consistently fewer [adverse] effects. Fewer severe [adverse] effects than chemotherapy. Thus, a well-tolerated treatment. It’s more just [for] awareness because when I think back to cases where things didn’t go so well, it’s usually delayed recognition or delayed action. Because if we see an immunotherapy [adverse] effect, an immune-related toxicity, we can often intervene, reverse those. But we need to identify those early. Those are [adverse] effects [that] we would want to hear [about] right away—where I want to get a call in the middle of the night [about] someone’s significant [adverse] effects. That’s not something I want to wait a few weeks to hear about.

You mentioned hypothyroidism. That’s much more common. A lot of these [adverse] effects are sort of on paper first, where we see them in the lab before. And it’s just important for oncologists to make sure we’re checking fairly regularly. But some studies will report even 1 in 5 with hypothyroidism. Fortunately, that’s one that’s easy to manage.

And one last thing about toxicity that I think has really encouraged both of us is that when we look at studies using checkpoint inhibitors, especially dual-checkpoint blockade, some patients have to stop for toxicity. And they stop before that 2-year mark. And it turns out that people that have to stop for toxicity do just as well, if not better, than people that continue and complete that full 2-year course. That 2-year course, while that’s our goal, is a little arbitrary. And if we need to stop earlier, we are very comfortable doing that, especially if we’re stopping for [adverse] effects. A lot of times if we stop for [adverse] effects, it doesn’t mean that we have to move on to something else. We can often just watch, and those are often patients that do quite well long term.

Neal Ready, MD, PhD: There’s a question in the chat asking for special populations like HPV [human papillomavirus], hepatitis B, hepatitis C. Is there any experience with treating those, and how did they do toxicity wise?

There are certainly some retrospective studies with pembrolizumab and other PD-1 checkpoint antibodies where there was no excess toxicity seen. And some patients had clear efficacy. It appears possible to do. CheckMate 817 was a large phase 2 study that ended up with a small number of patients with hepatitis or HIV.

Transcript edited for clarity.

Related Videos
Joshua K. Sabari, MD, an expert on lung cancer, presenting slides
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