Toxicities Seen in the Treatment of Lung Cancer

EP: 1.Understanding the PACIFIC Trial

EP: 2.The Role of Molecular Testing in Lung Cancer

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EP: 3.Toxicities Seen in the Treatment of Lung Cancer

EP: 4.Special Patient Circumstances and Immunotherapy

EP: 5.Immunotherapy in Non–Small Cell Lung Cancer

David Spigel, MD: I want to focus a little on the safety of immunotherapy in stage III cancer. In stage III cancer, the treatment plan can be a bit complicated when you go through this with patients at the beginning because it has so many different elements. We’re first talking about the stage of cancer, and that you don’t think surgery is the right kind of modality to use in their care. You’re thinking about your chemotherapy regimen in radiation therapy. Remember, in PACIFIC, any platinum-based chemotherapy doublet is considered reasonable. I use carboplatin-paclitaxel routinely. There is not a role for induction or consolidation chemotherapy in that trial. It was not something that was administered. Then transition to immunotherapy. There are a lot of elements here in terms of how you do all those.

Remember, pneumonitis is probably our No. 1 toxicity, along with esophagitis and mucositis. They come about from chemoradiation therapy, so that transition from the end of chemoradiation to the beginning of immunotherapy, for me it is predicated on how the patient is doing from a pneumonitis perspective and esophagitis. Because we want to be through that before we introduce something that could also cause that. We know the rate of severe pneumonitis was below 5%, probably closer to 3% with durvalumab in the PACIFIC study. But we know pneumonitis anyway, even all-grade pneumonitis, is relatively common with chemoradiation therapy. I try to make that assessment. I use imaging to get an assessment of how someone’s lungs look, how they’re feeling obviously...before we embark on...

As you go through a year with immunotherapy, remember you have all the things that can happen with immunotherapy, your flare with stage IV setting. We’re still watching for those toxicities—any of the inflammatory conditions that can occur with the colon, with the thyroid gland, with the kidneys, with the liver, and the pancreatitis, so all the usual assessments you’re doing in general. In my experience, if you get through that first transition period from chemoradiation to immunotherapy in a way where the patient doesn’t have any setbacks and there doesn’t seem to be an exacerbation of their pulmonary..., getting through the next year tends to be pretty straightforward.

When you have difficulty in those first 2 or 3 months in terms of starts and stops—using steroids and antibiotics for what you perceive to be bronchitis, possibly pneumonia—it does get hard to get people back on consistently and stay through that. Sometimes you do have to use steroids routinely to keep them off therapy for a year. But usually you know all this in the beginning. I think for the minority of patients who have not been able to get through a year of durvalumab, we figure that out pretty early on. Largely it was because of.... I tend to image patients about every 3 months with unresectable stage III disease. Once we start durvalumab, that’s the plan of care. Of course, if patients do well long term, I reduce the frequency of those evaluations.

I think 1 year is the standard simply because that’s the way the study was designed. You’ll see emerging data coming out from some ongoing trials. Look at that question a little differently. There are some studies designed to stop at a year, and some just keep immunotherapy going. That’s a strategy I’m hoping doesn’t become a new standard because for stage III cancer, you’re trying to cure somebody to have start-and-stop therapy and not have them be on that forever. Indefinite immunotherapy sounds more like treating stage IV cancer, but that’s really not what we’re trying to do here. We’ll see what those trials show. But in the PACIFIC study, what’s FDA approved is 1 year. We try to stick with that.

Transcript edited for clarity.