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, Chair of the Executive Thoracic Committee for SCRI, 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:
Thank you, Dr. Johnson. I'm Vamsidhar Velcheti. I'm a Professor of Medicine at NYU and the Director for the Thoracic Oncology Program.
Dr. Helena Yu:
Hi everyone, I'm Helena Yu. I am an Associate Professor of Medicine at Memorial Sloan Kettering Cancer Center in New York. Happy to be here.
Dr. Johnson:
Today we'll be discussing the treatment and management of non–small cell lung cancer with three patient case studies. Our second installment will focus on the management of stage IIIA non–small cell lung cancer in a former smoker.
SC is a 62-year-old female, 25-pack-year former smoker who presented with shortness of breath and cough. She had no prior medical history. Her CT scan is shown at the right, showed a right upper lobe mass measuring 5.7 by 2.6 cm. A single pretracheal lymph node measured 5 mm by 6 mm and the PET confirmed the right upper lobe mass to be FDG-avid as well as that pretracheal lymph node. Let's take this to our tumor board for discussion. Here are some questions that we need to cover. Who else needs to see this patient? What other tests do I need to order and is this someone that needs a mediastinoscopy? Maybe I'll start with Dr. Yu.
Dr. Yu:
All great questions. I think this is a perfect case for a multidisciplinary review because this is a very large tumor and really wondering about resectability and also being able to encompass the entire tumor and the mediastinum in a radiation field as well. So I think surgery and radiation oncology should definitely see this patient along with medical oncology. And then other testing that I think would be helpful would be—in a tumor this large, I actually like to do full staging, so I would do an MRI of the brain and then I'd want mutation testing and PD-L1 expression as well.
Dr. Johnson:
Dr. Velcheti, anything else that comes to mind?
Dr. Velcheti:
Yeah, I would add that I would probably not do a mediastinoscopy in this patient. We routinely do like a EBUS for staging, but in some parts of the country where access to interventional pulmonary may be challenging, it's not unreasonable to do a mediastinoscopy.
Dr. Johnson:
So this patient did go for a surgical consultation and the surgeon returned a call to me the same day saying, look, the resection that I would have to do is likely a pneumonectomy. And so he also was interested in his radiation oncology colleague seeing the patient. Radiation oncology spoke to the patient about chemo-RT to 45 Gy followed by resection.
The patient had PFTs showing that she was an operable candidate and FEV1 and FVC each was 65% predicted with a DLCO of 82%. And an EBUS—bronchoscopy with EBUS—was also performed that showed that all the lymph nodes in the mediastinum were negative. So the tentative staging at the end of our tumor board discussion was a T4N0 squamous cancer based on that bronchoscopy. The NGS was performed negative for all mutations with a PD-L1 level of 20%.
So back to the tumor board with all of this information, sometimes patients come to our center and then go back to their community site to be treated. We needed to discuss how many cycles of therapy if all the—is nivolumab the same as pembrolizumab, and when should we stop and image again to see if we can take this patient to the operating room.
Dr. Velcheti maybe I'll start with you.
Dr. Velcheti:
Yeah, I don't think at least I personally don't feel like there's much difference between either of the PD-1 agents. However, I think there's a little bit of difference in terms of the trial design with the CheckMate 816 and KEYNOTE-671. I think the optionality of being able to give adjuvant therapy after surgery is, I think, important and in regards to number of cycles, this is a patient that perhaps needs four cycles before consideration of surgery, especially given it's likely a pneumonectomy. So I probably would... That would also factor into the decision in terms of which regimen to use.
Dr. Johnson:
Dr. Yu, do you ever use four cycles or do you always stop at three?
Dr. Yu:
I like what Dr. Velchetti said. I think it sometimes feels uncomfortable to go through all three cycles without getting an early peek and seeing what's going on. And I don't love that personally. And so something like this with a pretty large tumor where I want to keep an eye on it closely, especially if I'm doing a four cycle regimen, I would image after two to get a sense. I don't want for those off cases where there's tumor growth, I'd like to abort and rethink a plan B before and just to give us some confidence if things are responding that we can finish through to all four cycles. And so that would maybe, and I do, I think because unfortunately most of our patients don't get major pathologic responses or complete responses. I think the extra cycle of chemo and then also the option to do some adjuvant therapy post-op are appealing to me.
Dr. Johnson:
Maybe I'll just play devil's advocate a little bit, push you a little bit further on that. Talk to me about why it makes sense to figure out sooner rather than later that you want to switch the plan. Why not do four cycles of chemo-IO and then do the radiation if you need to out back?
Dr. Yu:
If we're going to do definitive radiation, I would prefer to do definitive chemoradiation because the outcomes there are significantly better than with sequential therapy. So someone like this who at the outset we feel like could tolerate that, I would at least like to know at that two cycle mark because if I touch base with the surgeon and say, oh, now we see some vessel invasion, it's a little trickier, then I can kind of quickly segue and at least get a couple of those cycles concurrent with the radiation. So I think the earlier, the better for knowing about being able to have some flexibility to switch.
Dr. Johnson:
In this case, we did reimage after two cycles and there was disease response in that right upper lobe. Also, the 4R lymph node got smaller, but it wasn't enough to rule out that the surgeon was going to have to do a pneumonectomy. And we actually had two surgeons from competing health systems involved in this case. Both said that if they needed to undergo pneumonectomy and they knew that before they got to the operating room, then they would prefer to pull back and do chemoradiation to shrink the cancer and then think about resection in the future. But the patient was very motivated for resection, so we decided to do two more cycles and we cross our fingers and toes. After the third cycle, her shortness of breath and cough improved markedly, but at the same time, arthritis, fatigue, and neuropathy began to increase. So we all felt like that fourth cycle was definitely the last one, and we had pushed as far as we could.
At the time of resection the surgeon felt that he could get the tumor out with lobectomy, and so the patient underwent a right upper lobe lobectomy, which showed invasive, poorly differentiated squamous cell carcinoma. Approximately 63% residual tumor was noted. It was 5.4 cm at that time, actually. And that showed shrinkage from how it had looked initially. There was signs of adjuvant or treatment effect, there was signs of treatment effect. There was no plural invasion. The parenchymal margins were negative, 0.34 cm from the closest margin. The vascular and bronchial margins were negative and the level VII lymph node was negative for metastatic carcinoma.
So this patient was definitely downstage ypT3N0, but not a complete response. This patient had a disease response but wasn't a path CR or an MPR, major pathologic response. So what do we do next for this patient? Dr. Velcheti? Would you give more chemo? Adjuvant chemo? Remember the patient got four cycles of carbo taxol.
Dr. Velcheti:
Add more chemo. But certainly I think this is an unmet need, right? And patients who had minimal response, some response, but not as much as we would like to see. But I definitely would give this patient adjuvant immunotherapy. I mean there are obviously a lot of trials as you know, which are currently addressing this population. It'll be interesting space to watch.
Dr. Johnson:
How much adjuvant immunotherapy would you give?
Dr. Velcheti:
I would do a year of immunotherapy.
Dr. Johnson:
As best we know. Of course there was the Neotorch trial that did report three cycles of chemo-IO before one cycle afterwards, but the rest have really done the chemo up front for the most part, and then the IO out back. And this is somebody to us that also felt like she wasn't done. She did remarkably well, but she wasn't done. And that's hard to communicate to a patient. What's really, as the patient sits across from you in the examining room, how do you convey the right amount of optimism and excitement with also the right amount of, we got to keep going so that patients come to their appointments and adhere to treatment. Dr. Yu, anything else to add here?
Dr. Yu:
No, I mean, I just think with all of this neoadjuvant therapy, we have more information at our fingertips. We have the sort of in vivo response to chemotherapy and immunotherapy that we both previously didn't use in our decision-making, but I agree with you. I think whenever I see a significant amount of residual tumor in kind of a minor treatment effect, you want to give this patient more because you kind of know in your heart of hearts, this person probably is at risk for recurrence. And so again, I think having that information is even obviously more refined than our staging information. So hopefully studies will really be able to granularly tell us how to treat different patients based on this pathology data in the future.
Dr. Johnson:
It does make me think back to the PD-L1 levels. It's really easy to say, oh, well we don't really need that because we're going to give everybody chemo-IO. And remember, the first patient had a low PD-L1 score, but a high TMB. So the advantage of having both the NGS and the PD-L1 where the second patient had a PD-L1 that was low. And so maybe we should have known in retrospect, but it does help to prognosticate.
So the key clinical takeaways from case two are that we have increasing data that patients that are treated with this neoadjuvant chemo-IO approach have improved overall survival at 3 years and beyond as compared to the PACIFIC trial in which patients got chemo-RT followed by immune therapy and their 3-year overall survival rate's not quite as good in this stage III setting. So we should be looking for reasons to give chemo-IO upfront in concert with a surgeon that's willing to take that patient to the operating room.
Partnerships also with radiation oncology as well as thoracic surgery are critically important. And while it does fall on the medical oncologists often to be the glue between these physicians that may or may not sit together in an organized tumor board once a week, it does allow a better option for the patient if we extend that extra effort. And then finally, just a reminder that even T4 tumors can be completely resected after neoadjuvant chemo-IO. So remember that as you talk to your thoracic surgeons.
This brings us to the end of case two. Please see the other segments for further discussion about the latest research in non–small cell lung cancer or visit ascopost.com.
