Dr. Roy Herbst:
Welcome to the ASCO Post Roundtable Series, First-Line Immunotherapy for Metastatic Non–Small Cell Lung Cancer: Special Populations and Unmet Needs. I'm Dr. Roy Herbst, Deputy Director at the Yale Cancer Center. Joining me today are two of my colleagues. I'll have them each introduce themselves. First, Dr. Karen Reckamp.
Dr. Karen Reckamp:
Hello, happy to be here. I'm Karen Reckamp, the Division Director for Medical Oncology and Professor of Medicine at Cedars-Sinai Medical Center in Los Angeles.
Dr. Herbst:
Thanks, Karen. And Dr. Charu Aggarwal.
Dr. Charu Aggarwal:
Hi, everyone. Thank you for having me here. I'm Charu Aggarwal. I'm a Professor of Medicine, a thoracic oncologist at the Abramson Cancer Center at University of Pennsylvania.
Dr. Herbst:
Today we will be discussing the treatment and management of metastatic non–small cell lung cancer with three patient case studies. Our final installment will focus on the management of a patient with non–small cell lung cancer with brain metastases. I will now present this case. We have a 64-year-old man with left neck adenopathy. He's a former smoker for 10 years, 15 pack-years total. FDG, shown on the right, shows a large left upper lobe mass with left axillary, left cervical, and left mediastinal lymph nodes. There's a left lower lobe satellite lesion.
FNA of the left cervical lymph node is positive for non–small cell lung cancer of the adenoma subtype. The PD-L1, using the 22C3 antibody, has a TPS of 1%. Next-generation sequencing is performed with no actionable mutations. During staging workup and molecular testing, patient develops a weakness on his left side in his upper and lower extremity. Given the neurologic symptoms, the patient had an MRI of the brain, and as you can see on the right, the patient has metastases in his brain as shown. So before I go through the next steps, Karen, you have a patient with brain metastases, you can see the x-ray here, having symptoms. As you can see, the patient underwent surgical resection. Do you agree with that? It's a frontal brain lesion.
Dr. Reckamp:
In a patient with a frontal brain lesion and a solitary lesion, I do agree that surgical resection is a standard for these patients and has been shown to improve survival from data that dates back decades. But I think it is still the standard for a patient who could undergo, and it has good enough performance status to undergo, surgical resection, this would be the standard. And as far as the disease, often once they have surgical resection and radiation, we do think of this as looking at the systemic disease and determining how you might treat that, whether the brain met was there or not. But in this patient, they appear to have relatively diffuse disease with cervical lymphadenopathy, so would be ultimately thinking of treating systemically as metastatic disease.
Dr. Herbst:
Agree. And Charu, any other thoughts on the surgery? Could you use Gamma Knife for this or is it too big?
Dr. Aggarwal:
Yeah, I think depends on the center. I think in general, 4 cm has been our cutoff, or 2 cm in the brain has been the cutoff for Gamma Knife. I think certainly people push boundaries, and the question becomes how symptomatic is the patient? Does it really require decompression? Or how much edema is there to be able to really improve symptoms? So I think it's a combination of factors, but I agree with what Karen said, that I think it's important to come in with systemic treatment, but recognizing that local control here in the brain is imperative.
Dr. Herbst:
I agree. And as we said, the patient has symptoms, so it sounds like do the local control, but now of course, we're dealing with systemic disease. Let's just say for discussion, if the lesions were small, let's say we only had a 1-cm brain lesion, how would you treat that, Karen? Would you go ahead and do therapy and watch it, or would you use a Gamma Knife?
Dr. Reckamp:
So in a patient who has a small brain metastasis, 1 cm or less, that's asymptomatic, it depends on the biology of the tumor. For a patient without an actionable genomic alteration who won't get targeted therapy, I would generally still do targeted brain therapy, whether that be Gamma Knife or stereotactic radiosurgery in these patients. But I would probably not send him to surgery for that small of a lesion. For a person with a genomic alteration that might get targeted therapy, and without any symptoms, I would be comfortable treating with the targeted therapy and monitoring that brain metastasis.
Dr. Herbst:
Right. What about someone who has no actionable mutations, Charu? Can you use immunotherapy in someone with small brain metastasis? Does it work?
Dr. Aggarwal:
Yeah. And Roy, I think some of the data comes from your group, from Dr. Sarah Goldberg. I think there is data to suggest that immunotherapy alone may actually have efficacy. We at Penn have looked at our retrospective review. Of patients treated with immunotherapy amongst patients with brain metastases who may not have been treated with any upfront radiation therapy, we do actually see intracranial responses. This has also been shown in prospective trials using both bevacizumab and immunotherapy. So I think what we usually do is if they are completely asymptomatic, if it's small enough, not requiring steroids, I will initiate systemic therapy. I will loop in my radiation oncologist, I will make the patient and the radiation oncologist both aware that this is our plan, to initiate systemic therapy. And maybe we get another MRI at the end of two or three cycles and reassess. Or sometimes, depending on the location as well as the number of lesions, my radiation oncologist may sandwich the Gamma Knife in between the cycles of systemic therapy.
Dr. Herbst:
Right. You need to be creative. But now we've taken out this lesion, assuming the patient recovers reasonably well, now we have to treat the systemic disease, so adenocarcinoma. Karen, there's a PD-L1 of 1%, no actionable mutations. What regimen would you use here?
Dr. Reckamp:
So generally in this patient, I would use the carboplatin/pemetrexed/pembrolizumab KEYNOTE-189 regimen, it's the standard. And I don't know that we know whether the patient has any of the challenging mutations that we've discussed in the past, STK11, KEAP1, there's no actionable mutations. But again, as we've discussed, we don't know what type of NGS testing was done and what alterations were actually reported out. So I think it is important to know what alterations are on that report, even if they aren't actionable, and potentially thinking about other regimens. But in this patient, the way we know this patient now, I would use KEYNOTE-189.
Dr. Herbst:
Right. And Charu?
Dr. Aggarwal:
I agree. I tend to really think about KEYNOTE-189 as my key backbone here. But really, I think there are other options of course, but for somebody like this, limited cervical lymphadenopathy, we know there are no actionable mutations, PD-L1 is 1%, low. So I'm not using immunotherapy as a monotherapy, I'm also not certainly reaching out for doublet IO here, trying to minimize toxicity and maintaining that balance between efficacy and side effects.
Dr. Herbst:
Right. I would do the same, I think, in this case. And certainly you could consider other regimens, but that probably is the gold standard. And as you said, there are some data that suggest pembrolizumab can have activity in the brain, and we know that there's likelihood that there'll be other disease there in the brain if there was already that one lesion. So that sounds reasonable. Anything special about the patient with brain mets? How often, Karen, in a patient like this, treating with KEYNOTE-189, would you rescan the brain?
Dr. Reckamp:
Generally in these types of patients, we rescan the brain when we do our systemic restaging, and so that's somewhere around every 2 to 3 months in these types of patients with diffusely metastatic disease.
Dr. Herbst:
Charu, anything different at Penn?
Dr. Aggarwal:
I would not. I think for these patients, they're followed very closely by our neuro-rad onc group as well. And sometimes they actually prefer every-2-month scans. And after every-2-month scans, potentially at 12 months or sometimes at 24 months, they do change the frequency to 3 months. But they do like to follow these patients very closely.
Dr. Herbst:
No, absolutely. And have to do the physical exam as well as the radiographic exam. What about ctDNA here, Karen? Same answer? We had a similar case.
Dr. Reckamp:
Yeah, I think, again, ctDNA is very exciting and it's something that may be an adjunct, but at this moment in time, it's not for the clinic and wouldn't change my clinical decision-making about altering therapy based on the ctDNA.
Dr. Herbst:
Excellent. Any other final comments on this case, Charu?
Dr. Aggarwal:
I think upfront involvement of neuro radiation oncologists is key. Even if we decide not to treat the asymptomatic brain lesion, I think multidisciplinary management is really important, I think especially for this patient who may have limited burden of disease. If this patient was younger, I would be very upfront that, "Let's be as aggressive as possible. You've had your brain met resected, you only have cervical lymphadenopathy. Maybe we get creative and come in with radiation approaches." So I think upfront involvement and have an open mind about multidisciplinary management for these patients.
Dr. Herbst:
Okay. Well, just to summarize, we have a patient with adenocarcinoma, widely metastatic with brain metastases, symptomatic, frontal lobe lesion. The conclusion of our group is if you can operate, especially if the patient's having symptoms as this one did, do that. And if it's smaller, perhaps one could do a more limited procedure with Gamma Knife, radiation therapy, and then treat systemically. And for PD-L1 1%, we're hearing carboplatin/pemetrexed/pembrolizumab, the KEYNOTE-189 regimen, to be the choice of our group today. So I think that ends the discussion of this case, and please see the other segments for further discussion of the latest research in lung cancer or visit ascopost.com. It's really been a pleasure being here with you today. Thank you very much.
