High Hopes, Dashed Dreams: Progress in GI Cancers at ASCO

Mark A. Lewis


June 08, 2023

This transcript has been edited for clarity.

Hello. I am Mark Lewis, director of gastrointestinal oncology at Intermountain Health in Utah. I am speaking at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, where we have seen some interesting new data in gastrointestinal (GI) cancers that I'd like to tell you about.

One theme that sums up not only GI oncology but this entire meeting is that we have to take things that appear biologically plausible and promising and sacrifice them on the altar of data. The reason I say that is because I came to this meeting with high hopes, some of which have already been dashed. It's important to admit that the whole reason we do research and then talk about it is because not everything that we think is going to happen is borne out by the evidence.

I'm thinking immediately of a trial just presented yesterday at this meeting on the management of pancreatic cancer, specifically pancreatic adenocarcinoma. It is extremely well known that this is a deadly disease for which we know we have to do better.

Interestingly enough, one of the challenges that we face as clinicians is to determine the order of treatment we should be providing. There are two things about pancreas cancer that we need to reconcile. One is that it can only be cured in the operating room. The other is it is a systemic illness whereby surgery is almost never enough by itself. It's necessary, but not sufficient.

The trial that was discussed yesterday, the NORPACT trial, was looking at whether we should be giving chemotherapy before surgery or going straight to the operating room in patients whose cancers are clearly resectable. The results were frankly shocking because my bias was that I'm a medical oncologist, I give chemotherapy, so I think it would make sense to give the chemotherapy first for two reasons. In the best outcome, it allows the cancer to be shrunk down and easier for the surgeon to remove even if they deemed it originally operable. It also protects and prevents, hopefully, from metastasis.

By giving the chemotherapy first, I've always thought that we're actually selecting out the patients who are most likely to benefit from the surgery because if you have a patient who develops metastasis, that person is almost never going to see the operating room. The opposite already happens, where we take people to surgery first and we see them recur with metastatic disease, sometimes before they're even healed up from surgery.

That trial really takes us all the way back to the drawing board as to what order should we be going in. Should we be doing surgery first if the patient is clearly operable? Or should we be sequencing some form of chemotherapy first? Unfortunately, we still don't know. Outside the context of that particular study, there are other studies done in this area. We just don't have a clear answer yet. Watch this space. Pancreas cancer remains, unfortunately, a fearsome enemy for patients and oncologists alike.

Another trial that I was hopeful would mature in a positive way but did not was ATTRACTION-5. Immunotherapy has burst onto the scene in upper GI cancer in the past 2-2.5 years. Again, we've been experimenting as to what's the right sequence and the right context. ATTRACTION-5 was looking at the adjuvant role for nivolumab in gastric cancer, and unfortunately, it did not meet its prespecified endpoint. As appealing as that sounded, we also have to let that go.

Now, you might be wondering, Well, gosh, where is the promise here, Dr Lewis? What have you been excited about? Well, what I'm most excited about is that tomorrow on the plenary stage, there's discussion of the PROSPECT trial in rectal cancer. Rectal cancer has traditionally been the most and necessarily multidisciplinary cancer in all of GI because it has required, for decades now, a radiation oncologist, a medical oncologist, and a colorectal surgeon.

Again, we've been experimenting with the right order to go in. What the PROSPECT trial is trying to answer — and from its plenary presentation, the answer is going to be meaningful — is: Can we actually omit radiation in tumors that are very high in the rectum?

One of the messages of the past decade has been that the right and left colon are different. They're actually embryologically different. The left and right colon are, respectively, the hind gut and mid gut that fuse in utero, and they fuse in the transverse colon.

It gets even more nuanced than that because maybe we actually need to manage upper rectal cancer differently than lower rectal cancer. As a general rule, the closer you get to the anal canal, the more fixed the tumor will be in the pelvis and, arguably, the more of a role radiation might have.

Finally, I think this is the era of biomarker-informed care. I literally just came from a talk that was really exciting to me, which is the GLOW trial looking at an antibody called zolbetuximab for a selected population of esophageal cancer. By selected, I mean not the patients themselves, but the biomarker characteristics of their tumors. Here, it's really a case of you only find what you look for.

The analogy I draw is this: There is not an oncologist at this entire conference who would dream of treating breast cancer without knowing ER, PR, and HER2. Those are kind of the base amount of data that you need, the lowest common denominator. Yet, we do not apply those same standards in GI cancers. What I think I just learned at this conference is we have to be applying a similar rigorous standard of testing to our esophageal cancer patients; otherwise, we will miss the opportunity to treat them.

Zolbetuximab, this antibody, only works in patients that are high expressors of claudin-18.2. I know this just adds to the alpha-numerical soup of oncology, but I think the future is reflexive testing by our pathologists of these tissue specimens to let the oncologists glean the most value out of that testing. I liken it to if you're trying to wring a wet rag and get every last drop out, in terms of information, that's what we want to be doing with our tissue.

I think the future is a more perfect union of pathology and oncology, ideally with reflexive testing based on the diagnosis. We know, just by human nature, by cognitive bias, that it's actually much harder to opt into something than it is to opt out. A good example is organ donation. In countries where you have to opt out of organ donation, they have extremely high donor rates. In states and countries like ours, where almost everyone has to opt in, those rates are very low.

I think to unburden the oncologists a little bit but also to lean in to everything that pathology can tell us, we're going to need some reflexive order sets where the pathologists can run these biomarkers, many times before we've even met the patient, so we can craft a truly personalized set of treatment recommendations just for them.

Those are my thoughts about this particular conference. I've really enjoyed being here. For those of you who aren't here, the energy is palpable. It always feels to me like progress happening in real time just not fast enough for all our patients. That is also a clarion call that we need to be treating them with the fierce urgency of now.

This is Mark Lewis coming to you from the 2023 ASCO Annual Meeting in Chicago.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City, Utah. He has an interest in neuroendocrine tumors, hereditary cancer syndromes, and patient-physician communication.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.