Chapters Transcript Video Metastatic Disease: Management of Toxicities So, um, management of toxicities is, uh, it feels a little bit like I'm speaking to the, uh, preaching to the choir here, but, um, we'll dive a little bit, uh, specifically into immunotherapy and antibody drug conjugates today. These are my disclosures. So why does this matter? Um, as, you know, we've heard today, you could probably, it's probably easier to say who doesn't get immunotherapy, uh, in lung cancer than to go through all of the different indications that we do give immunotherapy. So increasing use of immunotherapy and ADCs in, in oncology and, and lung cancer in specifically, with unique and potentially serious toxicities. And early recognition and management of these toxicities leads to better outcomes for our patients. So immune checkpoint inhibitors, everyone knows, uh, so target key regulators of the immune system, including PD1, PDL1, CTLA4, they restore T-cell immune, uh, T cell activity against the tumor. Um, so the toxicities that we see with immune checkpoint inhibitors look like autoimmune issues. Um, a non-exhaustive list here of some of our, um, ICIs here. So, again, common, um, ears that we see, um, particularly in lung cancer, pneumonitis is a little bit more common. We watch for colitis, which would show up as diarrhea. Um, some things we would, um, see first on lab abnormalities before patients might notice, uh, like hepatitis, nephritis. Endocrinopathies are certainly one of our more common events, particularly thyroid issues. So it may start as hyperthyroidism, transition to hypothyroidism, and patients are now on. A thyroid replacement hormone for the rest of their lives, adrenal insufficiency a little bit more serious, where we're now, um, having to replace, um, steroid in, in the patient. Um, some of the more rare but serious, uh, can include myocarditis, neurologic events, but the bottom line is that we need to be telling our patients, if you're noticing something different, you need to be calling in and letting us know, letting us tell you whether it's something you need to be worried about. So again, first part of, uh, your AE management is to recognize that it's happening, rule out other causes. These patients are obvious obviously have a lot of comorbidities when they're coming to us. They're smokers. Make sure they're not having a COPD exacerbation or pneumonia before you're calling it pneumonitis. Um, is it a GI bug, you know, ruling out other causes because, you know, common is still common. Once, uh, you do identify that it's happening, grading that toxicity, grade one, you might choose to continue treatment through. Um, uh, with some supportive care. So you could try Imodium first in, uh, someone who might have, uh, one or two loose stools a day. Um, if it's pneumonitis and it's showing up only on the CT but the patient's asymptomatic, you might choose to continue. Uh, grade 2 or higher, though, you should be holding immunotherapy and starting corticosteroids. Usually, we start at about 1 mg per kilogram per day. Escalating to 2 mg if needed. And if that EAE is grade 3 or 4, you should probably be at least thinking about admission for those patients. Uh, once the side effect has resolved to grade 1, go ahead and start tapering steroids, um, usually over about 4 to 8 weeks, about 10 mg per week. And you can consider rechallenging, um, with the immunotherapy once that, uh, Side effect has resolved, and you've largely completed your taper to make sure that the patient doesn't, um, flare again when, when off steroids. Uh, for those patients who are refractory, they've gone through one or two rounds of, of high-dose steroids, um, can't taper down. Uh, certainly specialist referral is appropriate, and use of second-line immunosuppression such as infliximab, mycophenolate, if it's colitis, you could consider something like vatalizumab, which works a little bit more locally to the colon. Um, and, of course, you would permanently discontinue immunotherapy at that point. So going into antibody drug conjugates, uh, targeted chemotherapy and antibody plus a linker plus a cyto cytotoxic payload, targeting tumor associated anti antigens, and the examples of currently approved, um, ADCs in lung cancer include trestuzumab roxatecan, certainly more, um, More, uh, use in breast cancer, but we do use it here in lung cancer as well for HER2 mutated non-small cell lung cancer. Uh, data DXD, which targets SROP 2 is currently approved for EGFR mutated non-small cell lung cancer and subsequent lines, and telicetuzumabvidotin, uh, for CMT overexpression. So for trestuzumab, droxoecan, um, again, these are cytotoxic payloads. So you get your cytotoxic, um, side effects like GI upset, nausea, vomiting, diarrhea, fatigue, alopecia can occur, rash and pruritus, musculoskeletal pain, as Neil talked about already, ILD and pneumonitis are something you should be watching out for, for in these, um, in these drugs as a class, uh, and left ventricular heart dysfunction can happen, particularly with refuzumabdroxycan. So having an echocardiogram at baseline. And is clinically indicated moving forward. Um, and again, cytopenias, increased LFTs, electrolyte abnormalities, you should be keeping an eye out for. Uh, Dapotumab drootecan, um, one of our newer to, uh, market drugs here. Um, stomatitis is, is one of the big ones that can happen with this. So, um, actually a recommendation to have patients chew on ice chips or have a popsicle, a cold drink while they're getting the infusion, um, using dexamethasone oral solution, um, it can also be helpful. Ocular toxicities also can happen here. So dry eye, keratiis, um, patients can use preservative-free lubricant eye drops, ideally, those ones that come in kind of the individual packets. Um, avoid contact lenses and should have an ophthalmologic exam at baseline and is clinically indicated if they start having any symptoms. Again, GI upset, ILD and pneumonitis, alopecia is a little more common with this one. Um, musculoskeletal pain and can have infusion reactions, um, which can be premedicated with diphenhydramine and, um, acetaminophen, and again, that your cytopenias and LFT abnormalities. For Taliauvi, um, again, a different payload here, so a little bit of a different, uh, profile. So, uh, peripheral neuropathy and peripheral edema are two of the big ones here. Um, you know, neuropathy, again, you're, you're going to likely dose reduce if you're, if you run into these side effects. Um, edema, you can manage with, uh, compression stockings, um, diureticscaut with cautiously, um. Fatigue, ocular issues, again, can happen with this one. So, same, uh, recommendation for ophthalmologic exam at baseline, um, GI upset, ILD and pneumonitis, infusion reactions, and cytopenias and increased LFTs. So, again, in summary, um, for immunotherapy, you're going to look for those autoimmune-like toxicities, treat early with steroids, ADCs, you're having more, you're more traditional cytotoxic chemo-like and target payload-specific effects. And so monitor closely. We need to be educating our patients on what to watch out for, collaborate across disciplines, and when in doubt, pause treatment and evaluate in order to provide best supportive care. And I am the only one who is under 10 minutes. I was Created by Related Presenters Carolyn Zawislak, PA-C Advanced Practice Clinician, Fox Chase Cancer Center View full profile
