Advanced Lung Cancer: A Year in Review - Episode 16

Stage III NSCLC: When to Start Durvalumab


Naiyer Rizvi, MD: Josh, do you do a baseline CT scan? Do you do it with contrast? How soon do you try to start the durvalumab? Do you have trouble getting patients through the first year of durvalumab?

Joshua Bauml, MD: I schedule a 4-week visit with me after the chemo [chemotherapy]/radiotherapy has been completed, and at that visit, they will have had a scan before they see me with a planned treatment chair that day. I think that a baseline scan is really important. I have had patients who did not have the scan at another institution and then the subsequent scan showed progressive disease.

Well, is the durvalumab helping, or is the durvalumab not helping? You do another scan, and now the cancer is getting smaller. So now I have patients with metastatic disease who are on durvalumab, for which it's not FDA approved, and that is sort of difficult to change because they're responding. When I tried to move up the scans and initiation of durvalumab to 2 weeks, which was within the forest plot, I saw way too much pneumonitis.

Leora Horn, MD, MSc: But we start a lot of patients between 2 and 3 weeks, and I haven't seen that. So I'm going to start looking for that.

Tim Kruser, MD: That ends up being kind of a hot topic, how early to really push it, and I'll say I don't put a ton of stock in the earlier starting of treatment performing better. I imagine some of that is just patients who are in better shape can also start it earlier. So if someone is having any kind of complications after chemoradiation or having any difficulty recovering, I do still try to get them to recovery before starting durvalumab as well. But I like this structured 2-week, 4-week, everyone coming in and getting a scan, and Josh having them set up for treatment that day. I like that structure that you describe, but I don't feel anxious about getting them treated earlier either.

Naiyer Rizvi, MD: And what is your chemotherapy regimen; do you ever give it sequentially for patients who can't tolerate concurrent treatment?

Tim Kruser, MD: Well, I mean as far as the chemotherapy/radiation, I think the concurrent cis [cisplatin]/etoposide or carbo taxol [carboplatin taxol] are both fine. I agree with Leora's statement earlier about weekly carbo taxol and now not doing the 2 consolidation doses, which was my practice previously, and it's nice to be able to drop those because that ends up adding more toxicity. The weekly is pretty well tolerated, and then starting durvalumab.

I'll say to the earlier question, I do tend to see more problems pop up or adverse effects from ongoing durvalumab through a year, and it's not uncommon for me to have to hold a dose and sometimes put people on steroids for pneumonitis. So I am seeing more adverse effects from that as well.

Joshua Bauml, MD: Speaking of adverse effects, just in terms of what we were discussing before, I don't know that we can reliably say that some pneumonitis is radiation induced. Some of it is I/O [immune-oncology] induced. If you look at the work by Dr Naidu, which looked at the radiographic features of pneumonitis, it's highly variable. So I don't think we can say just because it's in this area, it is the radiation, and just because it's in these areas, it's not the radiation. I tend to treat it just as pneumonitis, which is treatment-related, and based upon your work, Tim, as well as prior work, I feel comfortable after the taper of steroids in the pneumonitis setting of re-exposing to I/O. The prior series found a rate of safe retreatment of about 75%, and that's consistent with what your real-world data showed, Tim, of 80% that we can safely go back on. The 1 exception is that if someone is really, really sick, requiring the ICU, okay, maybe I shouldn't do that, but in general I've had good results being able to re-expose patients to I/O.

Naiyer Rizvi, MD: And, Tim, tell me about the radiation dose. Wasn't there some recent data that a high dose wasn't better than a lower dose or a regular dose in concurrent patients? What's your dose that you use?

Tim Kruser, MD: You're talking about RTOG 0617, which is a randomized phase III study looking at 60 Gy versus 74 Gy. And we as radiation oncologists like to think that more dose is always better. But actually the inverse was true and in pretty remarkable fashion. The five-year data just came out at JCO [Journal of Clinical Oncology], and the high-dose radiation arm was statistically inferior in terms of overall survival, by I believe 10% or 11%. So excessive dose in the mediastinum we know from numerous historical series causes cardiac-related morbidity and mortality, and we need to be judicious both in terms of localization of our fields but also radiation dose. So the other thing, in the current context, most people are sticking with 60 Gy, maybe 66 Gy if you've got a relatively modest volume of disease. But the days of pushing to 70 Gy and beyond, we’ve learned our lesson.

Transcript Edited for Clarity