Patient Profile 1: A 68-Year-Old Male with SCLC and Brain Metastases

Charu Aggarwal, MD, MPH: With that, I thought I'll bring a case to all of you. And we could talk about how each of us would think about managing this a little bit differently. This is a patient that I took care of. This is a 68-year-old male. Former smoker had an extensive smoking history of about 60 pack years. Had CAD hypertension, atrial fibrillation, routine meds to manage all these Astatin, Metoprolol, aspirin, presented with shortness of breath. And imaging revealed a large left pleural effusion, worsening pericardial effusion, and there was a question there may be possible early tamponade. Thoracentesis was performed. Flux placement was initiated and pathology from the plural fluid analysis revealed small-cell carcinoma. We went on and we performed further imaging. We found plural hepatic and brain m metastases that were confirmed both on pet scan, as well as an MRI. His performance status was great fully capable of doing all activities and shortness of breath had improved largely with the placement of the Flux catheter. We initiated therapy with carboplatin etoposide and durvalumab based on the Caspian study. And as you can see here, radiographic response was pretty brisk. There was a significant improvement in plural effusion. You see the baseline scans on the far left. We have post cycle 2 scans in the middle and then post cycle four scans. The pleural effusion, as well as the pericardial effusion improved, but also the significant reduction in disease burden or metastatic disease burden, I should say, which shrinkage of hepatic metastatic disease. And you can see very clear improvement and he continued to feel better, was breathing better, really had minimal toxicity from his symptoms. I'll tell you why I chose this regimen and then I'll open it to ask all of you. I thought that it was very important for me to come in with chemo immunotherapy. This is a patient who came to me in the outpatient setting. I could initiate treatment pretty quickly. We'll talk a little bit more about how we choose between the different PD-L1 inhibitors, but based on what we've seen, I thought it would be perfect to initiate concomitant, chemotherapy and immunotherapy. And I went with it, and it worked. And after that, he was on durvalumab maintenance for a while. Maybe I'll start with you, Vivek, how would you approach such a patient and tell me your management thinking?

Vivek Subbiah, MD: I would completely agree with what, what with the management of this patient, because here you have a patient who is, has pericardial effusion, who's progressing quickly. And as Taofeek mentioned earlier without starting anything, we would've lost this patient. And we know that cisplatin etoposide is our active agents used for the last 30 years. They do respond quickly and briskly, and you want to combine all the active agents for this disease. The management was appropriate. Absolutely completely agree.

Jared Weiss, MD: One teaching point here is the brain, right? The patient had brain metastases at baseline. And because this is such a chemotherapy sensitive disease, many of us clinically would start with systemic therapy, not radiate the brain first and wait for chemo. And, many of the trials in small cell required treatment of brain metastases before enrollment on First line trials and that that's changed now with the recognition that systemic therapy can be effective in the brain and can actually, for patients who are PS zero, who are asymptomatic from a neurologic perspective you can start with systemic therapy and follow closely.

Charu Aggarwal, MD, MPH: You raise a very good point. Do you usually sandwich whole brain radiation or radiation to the brain, I would say, in between cycles, or do you wait for the first four cycles? Tell us your preferred approach.

Jared Weiss, MD: If the patient's doing well, we'll continue to follow and watch. And if a patient has brain metastases, a diagnosis, we will monitor those as we would the rest of the body for response. If those are non-responsive and they can be somewhat less responsive than the rest of the body, then we would intervene earlier with radiation. But otherwise, I would complete the full course of chemotherapy.

Charu Aggarwal, MD, MPH: And then maybe at post cycle 4. How often I guess how often would you then continue to perform brain imaging after that? Let's say post cycle four, you came in, you had a very good response. How often do you continue brain imaging? And then I'll ask another follow up question after that.

Jared Weiss, MD: You want me to take that?

Charu Aggarwal, MD, MPH: Sure.

Jared Weiss, MD: I'm nervous if we have untreated brain metastases off chemotherapy. Andif we completed the 4 cycles of chemotherapy, the patient had a nice response in the brain. I'm worried that they're going to progress. I would think about radiation at that point. They're off chemotherapy, they're going on with their immunotherapy maintenance. I would consider doing it at that point. If you do not radiate at that point, you need to monitor pretty closely, like every couple of months to check for brain metastases and be on the outlook for new neurologic symptoms.

Charu Aggarwal, MD, MPH: Right. Taofeek question for you, do you do 4 cycles or 6 cycles of chemotherapy, immunotherapy? What's your preferred approach?

Taofeek Owonikoko, MD, PhD: Generally, for majority of the patients whether with, or without immunotherapy, I tend to just go for 4 cycles of platin double chemotherapy. And that is based on the fact that we never had any head-to-head prospective trial to look at 4 versus 6, but small data that we have in small cell and much more extensive data and non-small cell. We know that beyond 4 cycles, we don't get a lot of benefit. It's more toxicity, but having said, I want to take a step back to some of the questions you asked before and bring that back to the add addition of immunotherapy to chemotherapy. We all agree. That's it's a step forward, whether it's incremental or transformational, we can all argue about that, but for the patient that we take care of the way we also assess the level of improvement that we've witnessed, is important than when we look at it and say, well, it was only like 2 1/2 month improvement in media and overall survival. We actually do ourselves a great disservice in terms of where the field has been and where we are now. I tend to look at this more as what is the magnitude of benefit as opposed to measuring the month, but more appropriately in terms of the hazard ratio, which is difficult to discover with a patient at least in an academic setting, like this is important that we bring that out, that adding immunotherapy to chemotherapy reduce the risk of a patient dying of the disease by almost 30%. Now, for non-small cell, if we say that a lot of drugs got approved based on that magnitude of improvement and even less than two months improvement going back 15, 20 years ago, small cell suffers from the small bladder syndrome because it's in the chest with non-small cell and we've made so much advances with non-small cell that immediately, we now expect small cell to perform at the level that non-small cell is performing. Whereas it took us 20 years to get there. Which brings to point this case that you really used to illustrate what we do for our patient. A patient with non-small cell lung cancer, presenting like this, where we got fully to make the diagnosis, I think majority of us will take time to get additional tissue, to understand the biology of the disease better, and then come up with the more appropriate treatment, but over the past 3 decades, we've been satisfied with this approach of just make a diagnosis and then let me move forward because our initial treatment is going to work well just like it did here. The problem is always, when it stops working, then we don't know what to do. What is different? Why did that patient respond? With the effort in the field now we are very hopeful that we're going to find one single target, that's going to force all of us to have in a patient like this, to do a proper biopsy so that we can better understand the biology of the disease.

Transcript edited for clarity.