Key Considerations for Managing IO Toxicity in NSCLC

Julie Brahmer, MD, director of the Thoracic Oncology Program and professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, and David P. Carbone, MD, PhD, the Barbara J. Bonner Chair in Lung Cancer Research and director of the James Thoracic Center at The Ohio State University Comprehensive Cancer Center, share insights on managing toxicities of immune checkpoint inhibitor therapies in non–small cell lung cancer (NSCLC). In particular, they discuss the importance of acting early, distinguishing adverse events (AEs) associated with different agents, and what is being done to better predict the efficacy and safety outcomes in advances.

TRANSCRIPTION:

0:05 | BRAHMER: For physicians who are managing our patients on combination immunotherapy with chemotherapy, it's important to understand that and try to tease out what's being caused by chemotherapy and what is being caused by the immunotherapy, and not to hesitate to hold immunotherapy while we're trying to figure things out. I think that we see a slightly different AE constellation with the combination. Certainly, it's more likely to have colitis when you're adding a CTLA-4 inhibitor in combination. We certainly see more rash with that combination, and we can see similarly pneumonitis and other more rare [AEs] as well. But making sure that you understand that we can hold immunotherapy, but that even if we hold it, those [AEs] may take quite some time to go away, and we may need to use steroids or other disease-modifying agents in order to get the AEs under control. Certainly, there are certain situations where I may restart immunotherapy, but just use either nivolumab or durvalumab if I think that [AE] was mainly caused by the CTLA-4 inhibitor.

1:41 | I think in our lung cancer patients, we're always worried about pneumonitis, and certainly having a pulmonologist [who] is familiar with treating these patients and helping you treating them with steroids. But if you can't get these patients off steroids, or if they're not responding to prednisone or [intravenous] steroids, using other agents in the treatment of pneumonitis is the next step, whether it's IVIG, infliximab, or mycophenolate. Though, all those could be used if patients with pneumonitis are not responding to steroids.

2:24 | CARBONE: The most important thing is to tell the patient about what the possible [AEs] are and to tell the patient to communicate this to you immediately.

One of the most important AEs is colitis, and patients should be warned that if they start having unusual diarrheal bowel movements, not to sit and suffer at home, but rather to let you know immediately, so that you can intervene with the high-dose steroids in a slow taper, maybe infliximab, but if they let it get to an advanced state without letting you know or letting you intervene, you can have big problems.

I think that just education on management of AEs and appropriate and rapid intervention really make these regimens safe. In the context of a fatal disease like metastatic NSCLC, I think efficacy certainly justifies the possibility of increased toxicity for these regimens, especially in PD-L1 negative [disease].

3:36 | BRAHMER: The next steps, I think, are using ctDNA or other ways of telling whether or not a patient is at high risk of progression on these type of therapies, and then also using AI as well to better predict which regimen may be better for these patients, as well as also using ways to predict [AEs] or help monitor for [AEs] of these regimens. I think we're trying to get all of these patients to be able to be long-term responders and have their disease well-controlled for beyond 5 years, and we're seeing that now, and we're hoping to see even longer-term outcomes for these patients.

_{Image credits: Hands of chief medical officer ordering medicines online, typing on laptop – © motortion via Adobe Stock. Colored 3d chest ct scan showing left lung carcinoma, no air in left lung – © therads via Adobe Stock. Generative AI was used for some elements of this video.}