Monitoring Response to Therapy in NSCLC

Roy S. Herbst, MD, PhD, reviews indicators of relapse or progression of disease when monitoring patients on therapy in NSCLC.

Kristie Kahl: Next, I would like to focus on the monitoring response to therapy. What are the options for monitoring a patient on therapy? For example, what are some indicators of relapse or progression of the disease?

Roy S. Herbst, MD, PhD: It certainly is important in a clinical trial—and now in the clinic, because we have approved drugs—to make sure patients are responding or at least not progressing. For immunotherapy, like anything else, we use radiographs and we look at partial response, stable disease, or progressive disease, usually using RECIST [response evaluation criteria in solid tumors] criteria, measurements, and an x-ray.

Those can be somewhat confounding in immunotherapy patients because you can have what’s called pseudo progression. It might be the tumor is going to respond, but because of the influx of immune cells, the tumor looks bigger and not smaller on an x-ray. There are also some tumors that can take a long time to respond, so they might be stable for a long time or they might grow before they shrink; it’s a little hard to use that. The other thing about using x-rays is that sometimes the patient will get inflammation in the lung or have pneumonia or an infection. Now we’re getting even more sophisticated. We’re using ctDNA [circulating tumor DNA], so you can measure tumor burden through cell-free DNA in the plasma. That’s being done more and more. Then, of course, you have to look at how the patient is feeling and their performance status. Are they having any adverse effects? Are they up and about? All that put together would be something I’d use in my clinic in monitoring a patient with immunotherapy.

Kristie Kahl: How often do you monitor your patients?

Roy S. Herbst, MD, PhD: I still like to do it every 2 months. Some could probably go as much as 3 months. We’re talking about metastatic disease, but I usually do every 8 to 10 weeks I would get films. It depends on the cycle. It might even be 6 weeks if you’re giving the drugs every 3 weeks. I usually do 2 cycles after a couple of rounds. If a patient is stable or responding, maybe you can stretch things out. As we’ll probably talk about, these drugs can be given for long periods of time, so you want to minimize the number of tests the patient has to have.

Kristie Kahl: Does this monitoring vary by the type of therapy you’re using?

Roy S. Herbst, MD, PhD: Slightly, although most drugs are given on a 3-week cycle, either alone or combined with chemotherapy, so it would probably be every 6 to 9 weeks that someone would do this. You usually do restaging before you decide to give another round of therapy. ctDNA is becoming more common, though it’s not the standard of care. Clinical judgment is always there, as it should be.

Kristie Kahl: You mentioned pseudoprogression earlier. How big of a concern is that in non–small cell lung cancer?

Roy S. Herbst, MD, PhD: Not as much as 1 would think. There are probably more papers on it than cases I’ve seen of it. It’s 5% at max, but we’ve seen it. We’ve seen it here at Yale [Cancer Center]. We’ve written about it, so 1 has to be aware of it. But it’s not as common in lung cancer as it was in melanoma. Even there, it’s not that common.

Kristie Kahl: What do you do, though, when you suspect progression but aren’t sure? Do you continue therapy? Do we change therapy?

Roy S. Herbst, MD, PhD: If the patient is stable, I’ll keep them on immunotherapy as long as possible. If they’re progressing, you could use tools to determine if it’s an infection. Sometimes you could do blood cultures or bronchoscopy diagnostically. If you think it’s inflammation, you could get a biopsy. If you look at ctDNA, that quantitatively measures the free DNA floating in the blood, which would indicate if the patient is stable or responding, even though the tumor might look a little bigger, or you’re dealing with a pneumonitis, which is only high grade with these drugs in lung cancer, about 4% to 5%, but you can have a low-grade pneumonitis and other things that can be confounding for the response assessment.

Transcript Edited for Clarity

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