Dr. Janjigian:
Hello, and welcome to From Diagnosis to Durability: Elevating Outcomes in Gastroesophageal Adenocarcinoma at ASCO Post Roundtable. I'm Dr. Yelena Janjigian, medical oncologist and chief of GI oncology service at Memorial Sloan Kettering Cancer Center in New York. I'm joined today by two colleagues, Dr. Molena and Dr. Maron, who are part of our disease management team at Memorial Stone Kettering. We're discussing a second case today of a patient with gastric adenocarcinoma with oligometastatic disease.
So, by way of the case, this is a young man, 45 years old, presenting with a history of reflux, and then in a setting of melena and iron deficiency anemia. He had an endoscopy that showed gastric body tumor, and on pathology it showed poorly differentiated adenocarcinoma, with PET imaging showed gastric wall thickening, and clear evidence of retroperitoneal adenopathy below the renal vessel bifurcation. There's no peritoneal involvement seen on the laparoscopy that was done.
On biomarker testing, the tumor was MSS, PD-L1, CPS-50, HER2-negative and claudin-high, 80% overexpression by IHC 2 to 3+. So looking at the staging, Daniela, I know you see a lot of these patients in the clinic and it's such a difficult discussion because it seems like it's low-volume disease, but how do you think about them? Do you routinely do laparoscopies in these cases, and how do you frame the discussion with a multidisciplinary team?
Dr. Molena:
Yeah. A very, very, very good question here. Traditionally, retroperitoneal lymph nodes are being considered an M1 disease. So for the most part, in the past we've done only systemic treatment in these patients. However, in the oligometastatic setting, we do have those patients have a great response. And really, we are beginning to think about, maybe a more aggressive approach with these patients might lead to even cure or better disease control. And so as you know, in our DMT, these patients, I think it's important to discuss them so that we have a unified approach how to stage them and evaluate them before making the decision that should not be taken lightly, to do a big operation, a big resection on these patients.
For me, I think I like to have as much information as I can. So, definitely staging laparoscopy, definitely a PET. Sometimes I even get a brain scan on these patients because the last thing I want to do is do this big operation and find they have brain metastasis. So get as much information as possible.
And then I want to see a little bit that the disease has declared themselves over time. We want to really maximize the systemic portion of the treatment to maximize that micrometastatic control. And if they do well and the disease is stable or improved, then I am definitely willing to entertain, after a very thorough discussion with the patient... I don't really tell them that this is going to be definite a cure for them, but I like to discuss the option that we could do a more aggressive local treatment with surgery that would include resection on the primary site, including the metastatic site. And-
Dr. Janjigian:
Well, before we get to that point, do you biopsy the retroperitoneal lymph node at baseline?
Dr. Molena:
Yeah, I think that if there is a question, I would like to biopsy. For me, it's always-
Dr. Janjigian:
First staging.
Dr. Molena:
... first staging. You're never going to go back to it. It's only a diagnosis, that you can have a certainty the patient is positive. And since they change so much what you do, I think we should make an effort to try to get a biopsy.
Dr. Janjigian:
Steve, in a patient like this, clearly let's say he had an RP lymph node biopsy that was positive and the laparoscopy is negative. What is your preferred systemic option?
Dr. Maron:
Yeah, there's a question that comes up often. When I see somebody who has distant lymph node disease, I typically use a FOLFOX backbone, not FLOT, because I'm just worried that I can't give them FLOT for long enough to really see the disease biology. And then I think of what targeted and immunotherapies I can add in addition to this. So as part of standard of care for this patient, I would probably do FOLFOX with nivolumab because of the high CPS score. If I had access to doing zolbetuximab as well per the ILUSTRO data we saw in January, I would consider doing FOLFOX plus nivolumab and zolbetuximab.
Or if I had a clinical trial that allowed me to target both of these actionable biomarkers that the patient has, that would really be my utmost preference here with the idea that I want to treat them for a prolonged period of at least 6 to 9 months as aggressively as I can, and then reevaluate in our multidisciplinary team, is this a patient who has good biology, who we think would benefit from an aggressive surgery, removing a primary tumor, as well as all of their metastatic sites and really deriving this from the RENAISSANCE data where we saw that patients with visceral disease didn't benefit, but patients with lymph node only distant disease did have a survival benefit in a well-selected patient population treated aggressively.
Dr. Molena:
Well, I have to say, if I may comment on that-
Dr. Janjigian:
Daniela, how do you define oligometastatic disease?
Dr. Molena:
Yeah. So, we define it, there's really not really clear guidelines, but we want to have less than three sites of disease and less than five metastasis per site. So it's really a state where you have only limited extra local disease, not diffuse metastatic. And what I was going to say is that the RENAISSANCE only give perioperative FLOT. So let's keep that in mind. There was not a really aggressive systemic treatment, in my opinion. And so I would think that perhaps there is an advantage to other side, not just retroperitoneal disease, to do a more aggressive approach.
Now, there are some areas that cannot be resected. And so I am in favor of other forms of local control or local treatment. Like if you have a bone met, for example, you have a liver met that cannot be resected, I think that we should potentially consider doing radiation ablation, other forms of local treatment for that specific site.
And maybe I'm overly optimistic and I know that there is going to be-
Dr. Janjigian:
Well, it's uncharted territory and there's no data yet-
Dr. Molena:
Exactly.
Dr. Janjigian:
... but I understand your sentiment.
So, going back to the patient, actually was started on systemic therapy with FOLFOX nivolumab. And I agree, Steve, it's very tempting to add zolbituximab, and we've been able to do it occasionally in patients with private insurance, but this patient had a great response.
And in fact, on endoscopy, several biopsies, serial biopsies were done which were negative. And on the PET scan, it seems like at baseline, he had uptake in the primary tumor which resolved, and there was smaller retroperitoneal lymph nodes on imaging, also seemed to be responding, but of course, they weren't sampled. So you're in a situation where the patient had a complete clinical response on endoscopy at least.
And so how do you counsel those patients? Because he's young and wants to be aggressive. I think either one of you could start.
Dr. Molena:
I can start. That's a tough situation because you don't want to do a big operation and find there's no residual disease. You'll never know if you helped or not help.
But it's really difficult to assess every set of disease to see if there is any residual disease. So it's easier in the stomach or in the esophagus to get a biopsy. It's much more difficult to get a biopsy all the retroperitoneal nodes in this situation. I definitely restage. So PET, again, staging laparoscopy again, and potentially even brain scan again, just to make sure that there is no detectable disease somewhere else. And then I have a frank conversation with the patient and I make the decision together. I think definitely discussion of DMT and all. But at the end, I think it's important to have patient goals in mind and have patient participating in that discussion, whether they wanted to go for this major operation, they have some risk associated with it, or they want to go with a more surveillance approach. I think either way is probably acceptable if you do a very close surveillance so that you can operate if later on you find disease.
Dr. Janjigian:
And I think the critical time period is really not to do this too soon. I think we discussed this earlier and depending on different DMTs and patients and institutions, but at least 6 months to a year of therapy. And of course, you would deescalate the oxaliplatin and decide.
Steve, do you have a sweet spot when you consider this, or when you send the patients back to the surgeon timing-wise?
Dr. Maron:
Yeah. It often depends on the amount of the disease. I try to bring it up around 6 months and by the time we get all the other studies done, they're long past their oxaliplatin and we're usually hitting about the 8-month mark when they're hitting a multidisciplinary review, which is perfect. And I just continue their therapy at that time.
Dr. Janjigian:
That's great.
Dr. Maron:
And a lot of it that goes by the motivation of the patient. And just emphasizing that, look, there was evidence of distant disease in the beginning, I'm very worried that this is actually going to be a palliative resection in hopes of prolonging your life dramatically and giving you a chemotherapy-free period afterwards. But it's just challenging to definitively say that there isn't any other distant disease that we're missing in terms of setting that expectation.
Dr. Janjigian:
Exactly. And so this was a great case because the patient actually elected to go forward with surgery at 8 months, and he went through a retroperitoneal lymph node dissection. We usually have our urology specialists do that plus a subtotal gastrectomy. And interestingly, even though the primary tumor was complete clinical and pathologic response ypT0 with negative regional lymph nodes, there was residual cancer cells identified in the retroperitoneal lymph nodes. So, really demonstrates the value of surgical exploration even in the clinical CR settings. So far he's doing well. And again, it speaks to how far we've come with this disease, to Dr. Molena's point with combined systemic options.
So the clinical key takeaways from this case is that disease failure is typically distant. So we need to maximize systemic options and long-term combination of fluoropyrimidine platinum, occasionally a third drug if there's no biologic targets, but if there are targets or you can combine with combined immune checkpoint blockade, that would be preferred.
So upfront maximizing systemic therapy is crucial, so you can understand the disease biology and the path of the disease. Some of these patients develop rapid disease progression, and so this would not be good surgical candidate. Really, ultimately, we know we are palliating. This is ultimately metastatic disease, so it's unlikely that the patient will be cured, particularly if there's a clear visceral metastasis, but we're improving hopefully long-term survival and local disease control. And in distant disease and lymph node only consider 6 to 9 months of maximum systemic therapy, followed by educated decision by the patient, but also multidisciplinary evaluation for potential local therapy options.
This brings us to the end of this case. Please see the other segments for further discussion about the latest research in gastroesophageal cancer or visit ascopost.com.
