Managing Side Effects of New Treatments for Small Cell Lung Cancer

Defining the Small Cell Lung Cancer Treatment Algorithm Post-ASCO 2025 Hello and welcome back to the Oncology Brothers Podcast. I'm Rohit Ghossein here with my younger brother and Co host Rahul Ghossein. Today we are continuing our three-part CME series on small cell lung cancer. In the second episode, we are going to focus on adverse events and management available on treatment options available here in extensive stage small cell lung cancer. And for this, we are excited to have Doctor Misty Shields from the Indiana University. Misty, thanks so much for joining us. Speaker 2 Thank you. It's an honor and pleasure to be here. Speaker 3 Misty. Welcome, Misty. In our first episode we had a chance to touch on the current treatment landscape and the new data from ASCO 2025. Two back-to-back studies showing overall survival benefit. Here I am Forte for lupinectedin, anatisolozumab and Delphi for terlatimab. But this is all coming at a cost be a financial toxicity, side effects from the drugs, time toxicity and some significant logistic challenges when we're talking about Torlatimab. Before we take a dive into some of these common side effects and how to manage these, is it fair to say that your treatment algorithm for extensive state small cell lung cancer after ASCO 2025 in a patient with good performance status is going to be chemo immunotherapy upfront, then lobinectin immunotherapy as part of maintenance and at the time of progressive disease, you'll lean into terlatamab. Speaker 2 Yes, absolutely. So what an exciting year for ASCO here in 2025 to have these two amazing back-to-back sessions in the orals, you know wonderful data, exciting obviously as you mentioned with additional costs and logistics. So yes, I am automatically implementing these right as I got back from ASCO, you know, put a patient right on the and Forte regimen as they transition to maintenance immunotherapy. And absolutely I think that the algorithm as you outlined is, is completely accurate as to what I would do for my patients, you know, really addressing those logistics for Charlatimab, making sure it's fair and equitable access for all patients. But that is exactly the algorithm I would recommend for my patients who are have extensive stage small cell lung cancer. Speaker 1 Thanks for going over that Misty and yet again exciting times. We've seen oral survival benefit here as Rahul stated, and any oral survival benefit in this unfortunate disease is a win. Navigating Side Effects of Lurbinectedin and Immunotherapy in SCLC Starting off with in Forte here with lorbinexidine and immunotherapy. Can you touch on some of the common side effects that we see here and some clinical pearls around us? Though we have some experience with lorbinectidine because this was being utilized in second line prior to being used here in maintenance therapy. And also while you're going over side effect profile, there is some overlap that is seen with IO as well. How do you decide which one is causing those side effects and how do you maneuver through that? Speaker 2 This is such an important point. So as you mentioned, we had experience from the original study with the basket trial with Lerbnexton showing an objective response rate of 35% for patients. You know, automatically solidifying its place is an option for relapse cell lung cancer with superior response rate over tobetekin that has been historically used. So yes, we do have experience with it. You know, as Doctor Pasarez presented at ASCO, the hematologic side effects are, you know, and to be anticipated and what we saw with the addition of of lubinexidin to otezlismab and then Forte with that uptick of hematologic side effects, no surprise there. But you should really be cautious. And whenever you're thinking about this regimen, then the addition of GCSF for patients who are receiving lubinexidin to prevent that neutropenic fever, you know, there was not a large signal of it. But again, it was showing that aggressive supportive care upfront and helping patients, you know, counseling them, selecting them and ensuring that they have good hematologic reserve on this regimen. Speaker 3 And then let's see, going through some of those overlap side effects, be it through IO or Lubinectidin, we can see some liver toxicities. How are you deciphering which one's coming? Which are you going to stop immunotherapy, Lubinectidin both day-to-day in your clinic? What are you doing? Speaker 2 Yeah. So you're really wanting to watch those liver function tests really with an emphasis on the the bilirubin there, but not as much as in the the pan transaminases that we would expect with the pad of toxicity from immunotherapy. So really being able to tease out whether you see a cholestatic pattern or a transaminase pattern or a mixed pattern that should help you with the immune toxicity. Again, also if you're seeing fevers or other concerns for other immune related adverse events that may help you with the deciphering whether this is an IRA or liver nectin or combination. Again, you know, being careful with patients who may have liver metastases or underlying liver disease. You know, things like cirrhosis that you really want to be paid close attention to, close monitoring and and checking in often with your patients. Speaker 3 And I know you touched on the growth factors, you're someone who uses trilocyclib heavily in your practice upfront. This is something that I've not really adopted in my practice for all my patients. But if someone is on trilocyclib, when you switch to maintenance, lubenectadin and atizo, do you switch this to growth factors or is it safe to continue with trilocyclib at this time? Speaker 2 As much as I would love to continue the trial cycle, we haven't studied that just yet and I as you mentioned, I am a huge proponent of it. I do utilize trial cyclo, but my patients here in clinic it's meaningful, it's real. We see multiple phase two studies showing has benefit across multi lineage for hematologic toxicities and like helping patients reduce those toxicities such as you know neutropenic fever or hospitalizations that are very meaningful and dose delays and dose disruptions. And so you know it is important but the label is label. And so we have to follow how the original studies were utilized and that was in the pre Lurban accident maintenance era. And so I do switch my patients to a GCSF approach whenever I've come to the role of Lurban accident in the maintenance phase. Speaker 1 Before we switch on this topic of trilociclib, with regards to utilizing this approach, do you use trilociclib in all your patients or rather only on high risk patients? Speaker 2 So that's an important point. So I do use it in all patients. The only patients that I hesitate to use it online are patients who may have day 2 and day three PO or oral BID topocide. In that case, I use it in the first day and I don't offer it in those second and third days because it's given 30 minutes prior to each dose of chemotherapy. Speaker 3 Perfect Android, you touched on that. Overcoming Logistical Challenges and Side Effects of Tarlatamab We have some comfort around lupinectodin because we've been using this in second line. But when it comes to Terlatamab, I really think out in the community this is something that we need to get more comfortable with even though we're using bites for hematologic malignancies. Misty, can you touch on how are you partnering up with your community oncologist around this drug and managing that CRS upfront with the first few doses? Speaker 2 Yeah, absolutely. So this is important one, an exciting option for patients to have tarlatumab, this bispecific T cell engager against DLL 3 and CD3 for relapsed small cell lung cancer showing superiority in second line and beyond for small cell lung cancer. And so access to this should be equitable and fair. And so working with your community oncologist to make sure that they're, you know, considering referrals to you if they don't have access to it, if they have any concerns or feel uncomfortable managing it, that's what we're here for us to help support, to provide the best care for patients, whether that's at our center, at their center or in some combination. So, you know, really making sure that you know, if it, you know, phoning a friend if you need help, you know, there's a lot of academic oncologists who have access to this medication and have used it, such as myself, that are willing to help. And so with that, you know, we really think about that side count release being the highest in the first two doses, day one and day eight with that step in dosing. And so that's what warrants that close monitoring. The initial prescribing information from the label is 22 to 24 hours on days one and day 8. And if patients have any grade 2 or higher icons or CRS toxicity, they should have extended monitoring for those additional cycles. But I think we know once we get past that day 8, we're really seeing in our real world data that patients don't have the emergence of these side effects. And so I think that that should provide some comfort and ease for patients who might be in a community setting and those oncologists who might have, you know, hesitation or pause as to taking these patients either back or to starting this therapy in their center and then continuing those therapies in the outpatient setting. And, and what do we do with our nurses and our staff and our infusion times and, and how do we monitor these patients effectively? So I think if a patient demonstrates prior toxicity, you know, those are patients that should be on their radar or your tennis should be up to watching those patients closely. But if they've tolerated day one and day 8 historically, those patients are going to do well from that monitoring outpatient. And so I think that working together with your community and academic oncologists is key to provide the highest quality care for our patients and their families. Speaker 3 Absolutely. Speaker 1 Thanks so much for going over that. So just to summarize that, so the first cycle in general will be in the main institute and after the that has been administered at the mothership, they will follow an outpatient with community oncologist. Speaker 2 That's the idea. And so you know, really to have something in a hospital setting and that's, that's really the key. It doesn't have to be in an academic center, you know per SE, but it needs to be in an institution in a hospital setting that they're observed. I think as we study this more and that the data presented at ESMO IO in 2024 showed that there is some expedited and outpatient monitoring that could be done. And so I think we're we're moving that direction which would be wonderful for all of our patients and also to be able to treat more patients with this medication removing that rate limiting step. You know, but it really as it currently stands in the prescribing information, you know, we are looking at that 2224 hour and staying within an hour of the hospital in case any events occur outside of that window period. Speaker 1 I think that's the biggest logistical difference that every university or the hospital is deciding how to manoeuvre through that. So thanks so much for going over that. And now to what you stated, whenever the topic of terlatimab comes, the lot of discussion is around CRS. But again, once we have gone over this hump of logistical issues, other side effects are equally important. That is fatigue, taste changes, myalgias, and these are some of the common side effects that we would see out in community settings after we are over CRS. Misty, any clinical pearls around these? Speaker 2 Absolutely. Thank you for highlighting these. I think they're they're meaningful for our patients and their families. You know, really discusia can be pretty serious and so monitoring it, get it, catching it early and really being preventative and proactive. So having your patients who are on tarlatimab meeting with those patients early with dietary advice with your oncology nutritionist, that is the key. You know, adequate hydration, there's some paroles and practical management from tarlatimab that was provided by the investigators who studied this. But in my own practice, you know, really making sure that you keep it a diarrhea log with your patients of what things work, what things don't work. And, and to keep evolving and keep changing because it does change based on toladimab hitting those cluster 2 taste buds. And so it is meaningful, it is real and it's, it's a side effect that's with this class of drugs to be expected. You know, with the myalgias, again, this is very real. It should not be dismissed and should be addressed to also having your patients either if you're managing their pain or if they're established with palliative care, which I highly encourage early on to help support patients to provide the highest quality of care. That additional layer support. You know, providing palliative care referrals early for for patients with small cell is so meaningful and really helps them stay on treatment longer and stay out of the hospital with other, you know, events, things like fatigue. This is very real. And so getting your PTOT, you know, getting patients with light exercise, pulmonary rehab to help them stay on treatment longer and not have that ability from the wear and tear of treatment, including torolatumab is so important. Speaker 3 You know, the treatment here is with palliative intent, so that's supportive care. Educating our patients upfront to make sure that we're keeping that quality of life at the center of all this is so important. Essential Supportive Care and Immunotherapy Side Effect Management And then as we're talking about side effects, last but not least, we obviously have to keep side effects that come along with our immunotherapy agents here, though out in the community, we've been using this now over a decade, and there are arguably better tolerated than chemotherapy. That said, every single time I'm consenting my patient for this, we have a conversation around potential common side effects like thyroid abnormalities, rash or pneumonitis versus some rare side effects, right? CNS abnormalities, myocarditis or nephritis. These drugs are not benign mistake. Before we close, any last thoughts around the recent data from ASCO 2025 or supportive care tips for our listeners when taking care of small cell lung cancer? Speaker 2 Absolutely. So what an exciting time for small cell. You know, the landscape for treatment for first line maintenance and relapse for small cell lung cancer is rapidly changing. So checking your guidelines, checking in with any of your academic colleagues, seeing if there's any trials that we can help improve on the, the successes we've already made. We know that, you know, within Forte lurban accident in the maintenance setting should be considered, should be supported and should be closely managed With tarlatimab. Really, if you don't have access to it, finding the closest center that does and having a good relationship so that you can provide that opportunity for your patients or to get that at your center because this is here to stay. So I think, you know, early palliative care, early support, watching your labs closely, checking in with patients, not having a three month follow up, but really, you know, closely watching them having a toxicity check, having a lab check. I mean, meet with your nurse practitioner, PA or with your clinic to have, you know, a visit to make sure they're doing well on therapy, there's no new symptoms. They really want to support patients with small cell and close monitoring is absolutely key, especially in that transition to immunotherapy and on relapsed therapies like tarlatimab. We want patients to live longer and to have a success stories. And I think that the median is continuing to change and that tail the curve is lifting. What an exciting time for our patients and their families. Speaker 3 You know, we keep saying what an exciting time and we're looking at three to four month overall survival benefits. So it's not a home run, but it's a step in the right direction. What you said, this small cell lung cancer is a devastating disease. So again, any overall survival benefit here is meaningful. Missy, thanks for walking us through on what to look out for and how to manage some of these common side effects that we will see with these new indications for our listeners. Make sure to check out our first episode of this series where we touch on the current treatment landscape for extensive state small cell lung cancer. And stay tuned for that last episode where we touch on the unmet needs for this disease. Thanks for joining us. We are the oncology brothers.