Traveling Through the Lung Cancer Treatment Paradigm: Managing irAEs With Corticosteroids

In this fourth episode of OncChats: Traveling Through the Lung Cancer Treatment Paradigm, Aaron Franke, MD, of University of Florida Health, discusses the management of immune-related adverse effects (AEs) and the goal of mitigating steroid use for patients with lung cancer.

"One of the points of contingency is the use of corticosteroids in patients [with lung cancer] receiving immune checkpoint inhibitors. I know we have accumulating data that, to date, show there does not seem to be a noticeable detrimental effect in terms of the treatment efficacy in patients receiving steroids.

These patients, especially with dermatitis and some of these endocrinopathies, who have mild to moderate immune therapy–related AEs tend to have better responses and maybe better outcomes as long as there’s not a detrimental mortality to the AEs [themselves], like with pneumonitis or colitis. So, whether these patients who receive steroids or not, [whether] their survival is not pushed over or influenced by the steroids may be a surrogate for their biological activity to begin with. We know that most of these studies did not allow patients who were on chronic steroids above 10 mg daily equivalent of prednisone. How much data [do] we have to really parse through to say that patients did not have a detriment in the setting of receiving corticosteroids?

I think one part of this we're forgetting is that the chemotherapy regimens themselves, the paclitaxel without the [nab-paclitaxel (Abraxane)] version of it, or even pemetrexed, where we give 3 days of over 8 mg twice daily of dexamethasone, which again, is not an insignificant dose of prednisone to give for 3 days. I have adopted from institutional studies, where they had given a single dose of steroids, dexamethasone 12 to 16 mg on the day of chemotherapy. Now, I think there about 3 retrospective studies where they looked at patients who got the 3 days of dexamethasone vs the single day of dexamethasone for the pemetrexed chemotherapy premedication at least, and the rate of rash was about the same; it was less than 4% or 5%. Again, I really don't see much in the way of pemetrexed [and] rash. I do believe that giving less total steroid dosing, both duration and total dosing, is something that in my mind helps protect the patient a little bit against upregulating this T-cell immunosuppressive environment where we're upregulating the T regs and downregulating the cytotoxic T cells.

The other end of this story is, when we saw the upregulation of interleukin-6 inhibitors and tocilizumab [Actemra] used as COVID-19 protocols during 2020 and 2021 in patients who were on immunotherapy, or those who were having immunotherapy[-related] AEs that ended up getting tocilizumab as a byproduct of having COVID, or even those treated in the setting of having an immune-related AE, there seems to be a synergistic or better outcome in terms of their oncologic end points vs steroids. You can look at retrospective institutional studies and gather that despite the lack of data in the prospective phase 3 studies, there is a story to be told where we are not doing good biologically by having the need for steroids or maybe an unnecessary amount of corticosteroids in the regimen for patients who are on immunotherapies.

Going forward, [we are] trying to treat immune-related AEs and thinking about things as small as chemotherapy protocols with steroids involved and trying to mitigate as much use of that as we can. We're going to see the story play out. Even if it's only of mild significance, I think it is something that is biologically where I am in the school of thought that we are doing a harm to what we're trying to upregulate in the tumor milieu in the microenvironment.

I'm looking forward to alternative immune-related AE treatment protocols, as well as alternative chemotherapy premedications, where we can mitigate or eliminate steroid use."

Check back next Wednesday for the next episode in this series.