Managing Adverse Events in Patients With Advanced RCC Receiving an IO/TKI Combination Regimen
Dr Moshe Ornstein details the adverse events seen with IO/TKI combination regimens in patients with advanced renal cell carcinoma and the best strategies for management.
Robert Motzer, MD: So, in terms of the management, and I think we'll just touch on this briefly with TKI-IO combinations. Regardless of the particular TKI, what are the predominant adverse events that clinicians should be aware of with the TKI-IO combinations as they treat these patients and counsel their nurses to be aware of? Dr Ornstein, what toxicities do you see as predominant for TKI-IO combinations?
Moshe Ornstein, MD: This is a really important point because this will show up regardless as to whether we're using cabozantinib plus nivolumab, lenvatinib plus pembrolizumab, axitinib, and pembrolizumab. And I think there's a lot of discussion about what the specific toxicities are. And really the discussion is, we know that there are TKI specific toxicities, whether it's diarrhea, hand-foot syndrome, fatigue, etc. And then we know that there are immunotherapy toxicities, which are well established because we're giving checkpoint inhibitors in nearly every cancer. And those I think there's established guidelines and resources in terms of how to manage them. What do we do in terms of dosing for TKIs supportive care for patients who have hand-foot syndrome, mucositis, or diarrhea? At what point do we initiate steroids for immunotherapy toxicities? The challenge and the piece of education here is about those overlapping toxicities. So, if a patient is on axitinib and pembrolizumab and shows up to clinic with diarrhea and you're not sure if the diarrhea is being caused by the axitinib or the pembrolizumab, or a patient shows up with elevated LFTs and you're not sure whether that's driven by an immune-mediated event or by a TKI-driven toxicity. And the general management strategy that we employ is obviously if a patient comes in with a fulminant diarrhea that is classic for an immune-related colitis, that patient needs steroids. But most of these toxicities will start out as a grade one or a grade two, and there's a little bit of time that the patient has to sort this out. So, a simple strategy is just to hold a TKI for a couple of days. So going back to the diarrhea example, the patient shows up with four or five bowel movements above their baseline and you're categorizing them as a grade two. If you hold the TKI after a few days, if it is indeed driven by the TKI, you expect the diarrhea to get better, and then you manage the diarrhea, dose reduction, supportive care, etc. If it's not getting better, it's more likely related to the immunotherapy agent and you manage accordingly. And this really works across the IO/TKI regimens. Obviously, with the shorter half-life, it might work better for axitinib and pembrolizumab, but really across the boards for LFTs, even for fatigue, for diarrhea. Holding the TKI and letting things play out for a couple of days while managing the patient and monitoring them closely can really help us differentiate whether a toxicity is coming from an immunotherapy agent or from the TKI. And that's really the message to the practicing oncologist who may not see this every day, is there's usually time hold the TKI and take a couple of days to sort it out and let it in some ways really declare itself.
Robert Motzer, MD: Well, those are really great points for a critical topic for community use and management for patients with advanced RCCs.
