Dr. Melissa Johnson:
Welcome to The ASCO Post Roundtable Series on Optimizing Outcomes for Patients with Locally Advanced and Metastatic Non–Small Cell Lung Cancer. I'm Dr. Melissa Johnson. I'm the Chair of the Executive Thoracic Committee for SCRI, the Director of the Lung Cancer Research Program and a founding member of SCRI Oncology Partners. Joining me today are two of my colleagues. Dr. Velcheti?
Dr. Vamsidhar Velcheti:
I'm Vamsidhar Velcheti. I'm Professor of Medicine at NYU and Director for the Lung Cancer Program. Thank you so much. Delighted to be here.
Dr. Helena Yu:
Hi, everyone. I'm Dr. Yu. I am Associate Professor at Memorial Sloan Kettering Cancer Center in New York, New York, and also delighted to be here.
Dr. Johnson:
Today we'll be discussing the treatment and management of non–small cell lung cancer in three patient case studies. Our first installment will focus on the management of locally advanced non–small cell lung cancer.
Mr. JB is a 62-year-old male, 45-pack-year former smoker. His past medical history is significant for diabetes, stage 3 chronic kidney disease, and COPD. He presented with shortness of breath and cough. Chest CT, the images that you see on the right-hand side of your screen demonstrated a right lower lobe peribronchial thickening, atelectasis, and tree-and-bud opacities, as well as an enlarged subcarinal lymph node, about 3.5 by 2.4 cm. On PET scan, that same subcarinal node and right lower lobe pulmonary nodule showed FDG avidity and there was also right perihilar thickening.
A bronchoscopy was performed that showed squamous non–small cell lung cancer at the level of 4R and level 7. NGS and PD-L1 testing were obtained. PD-L1 expression was low at 15%, although his TMB was high, 19.2 mut/Mb, he had a KIT amplification, FGFR amplification, PIK3 amplification, and this tumor was MSS. The case was presented at tumor board. Maybe we'll pause here to begin our discussion. Maybe I'll start with Dr. Velcheti. A T2aN2 squamous cancer. Prior to 2022 when chemo-IO was first approved, what would your tumor board at NYU have recommended for this patient?
Dr. Velcheti:
I wish I could say clinical trial, CheckMate 816 or KEYNOTE-671. But as you know, the care paradigms for locally advanced non–small cell lung cancer pretty varied across the country and mostly because of access issues and access to thoracic surgeons like minimally invasive thoracic surgeons and obviously variations in terms of clinical practice patterns and access to pulmonary colleagues for adequate staging upfront. So there a lot of factors to consider, but for somebody like this with T2aN2 who looks like, based on the imaging, looks like it could potentially be a lobe, it's slightly central. It's hard to say, but it looks like it may be a lobe. It's not a huge tumor and looks like minimal mediastinal adenopathy. So probably this is somebody I probably would've done chemo-RT with an intent to take to surgery. But of course now we have more data with the new adjuvant chemo-IO trials with CheckMate 816 and also KEYNOTE-671. So I probably would not do that right now. I'd probably offer chemo-IO to this patient.
Dr. Johnson:
Dr. Yu, any differences in practice patterns with your tumor board either before or after March of 2022?
Dr. Yu:
Yeah, I think that this is such an interesting question. I think if you go to different centers for stage III disease or any locally advanced disease, you really get different answers and kind of depends on where you trained and where you are now. So at MSK, we don't do sort of preoperative chemo RT, so we kind of go down the path of resection or definitive chemoradiation right at the outset. So when looking at the case for me, the N2 nodes are relatively bulky at 3.5 cm and there were two positive stations. And so usually, honestly, multistation N2 disease, certainly pre–chemo-IO, we would've sent this person to concurrent chemo-RT. And then as Dr. Velcheti had mentioned, I think post we’re much more, I think lenient might not be the right word, but we're open to trying chemo-IO in patients with more advanced disease.
Dr. Johnson:
Yeah, let's move forward because of course, this patient was treated in late 2023, and actually we decided for chemo-IO, three cycles. The patient had a squamous cancer, and so he received three cycles of carboplatin, paclitaxel and nivolumab according to the Checkmate 816 trial data. His course was complicated by anemia and thrombocytopenia after every dose, and it required dose delays, blood transfusions. I finally had to dose reduce in the third cycle in order to feel as though I could treat him safely. Which brings up an interesting question, Dr. Yu, maybe I'll start with you. Do you think about dose delays differently in the neoadjuvant setting than you do say for a patient with metastatic disease?
Dr. Yu:
I think that it's a good question because of course in metastatic disease, our kind of treatment goals are palliative vs in this setting where we're trying to get someone to a curative resection, I don't necessarily change my behavior. I mean, I think we use, if someone seems to be high risk, and certainly with the use of carboplatin, I might use growth factor support to help with the neutropenia, but here with the anemia and thrombocytopenia, you're really, you need the marrow to recover. So I would've done exactly as you did. I think we delay. And then absolutely, I think if it sort of is coming to a head, I don't have any problems with dose reduction in this setting. But yeah, I think there's always a little bit more of a nervousness to delay and kind of further back out surgery. But I don't treat anything particularly different.
Dr. Johnson:
I did go to the NCCN Guidelines last night to make sure—you mentioned growth factor support, and of course for patients that are getting chemo-RT, we worry a little bit more about growth factor support and have for patients getting treatment for stage III cancers. But in this case, even if it is a stage III cancer in the neoadjuvant setting, the NCCN says that this is a regimen that has moderate risk for count suppression and cytopenias. And so growth factor support is allowed and recommended even. Now, the best news ever is when one's neoadjuvant therapy results in downstaging of the patient's tumor. And that was the case for this gentleman, JB, where the path at final resection showed a complete response to therapy. Dr. Johnson's first complete response after a lot of trying. So this opens up another chapter in this patient's treatment course, and that is in the adjuvant setting. So we've given three cycles. We've got a complete response at the time of resection. What do you do now? Dr. Velcheti, what would you recommend to this patient?
Dr. Velcheti:
Yeah, I think this is a really good problem to have. We don't have, at this point, we don't have ways to select adjuvant therapy post–chemo-IO. Of course, the CheckMate 816 had only the new adjuvant three cycles of chemo-nivo or chemo and nivo and no adjuvant approach. But again, we've seen the data, the subgroup data, like in patients who have achieved a complete pathologic response, they did really well with very low recurrence rates. And we see that in CheckMate 816 and also in KEYNOTE-671 and other trials as well.
So there's certainly, it's reasonable to just watch without any adjuvant therapy here. But again, part of me also, I'm a little worried because this is a patient who had such a great response to chemo and IO. Would three cycles just be enough, would maybe give a few additional cycles of IO post surgery. But again, that's very theoretical. We don't have answers right now. I know there are trials currently ongoing looking at personalizing adjuvant therapy approaches based on responses at the time of surgery. So we just don't have that information at this point. But for this patient, I probably would just watch.
Dr. Yu:
I think the flip side is so much more of a conundrum when we see lack of a good response and we review that pathology with our patients and they're kind of like, that's it, doc? It was still there, that I think it's hard with CheckMate 816, as you said, Dr. Velcheti, there isn't anything after, even if the response is not a major pathologic response or complete response. And so that does feel unsettling. And so I think I'm looking forward to those studies that will have sort of risk adaptive or pathology adaptive post-resection treatment options for our patients.
Dr. Johnson:
I think this rounds out this discussion of case 1 and Mr. JB really nicely. Some key clinical takeaways are that the CheckMate 816 trial as well as KEYNOTE-671, demonstrated that the addition of immunotherapy to chemotherapy improved the chance of event-free survival by a median of 10 months and resulted in path CR rates, so no more cancer 24% of the time with chemo-IO vs only 2% with chemo alone. Just like Mr. JB, tumors with N2 lymph nodes may be completely resected, even if there are N2 lymph nodes at more than one station, which is different from how we used to treat patients with chemo-RT. And the data is still unclear about the benefit of additional adjuvant therapy for patients with complete responses since only 20% of patients treated in CheckMate 816 received additional adjuvant therapy according to investigator discretion.
Thanks for joining us. This brings us to the end of this case. Please see the other segments for further discussion about the latest research in non–small cell lung cancer, or visit ASCOPost.com.
