Leveraging Immunotherapy in GI Malignancies: Is Multicancer Early Detection Becoming a Reality?

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EP: 1.Leveraging Immunotherapy in GI Malignancies: Is Multicancer Early Detection Becoming a Reality?

EP: 2.Leveraging Immunotherapy in GI Malignancies: Assays for Early Detection and Prevention

EP: 3.Leveraging Immunotherapy in GI Malignancies: A Shift in Drug Discovery

EP: 4.Leveraging Immunotherapy in GI Malignancies: Research, Including Organoids and Ablation

EP: 5.Leveraging Immunotherapy in GI Malignancies: Looking to the Future

In this first episode of OncChats: Leveraging Immunotherapy in GI Malignancies, Toufic Kachaamy, MD, of City of Hope, Sunil Sharma, MD, of City of Hope, and Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, discuss the potential for early detection multiomic assays and the work that still needs to be done to encourage their widespread use.

Kachaamy: Hi, this is Toufic Kachaamy. I am the chief of medicine and the director of gastroenterology at City of Hope in Phoenix, Arizona. I’m joined today by Sunil Sharma, MD, and Madappa Kundranda MD, PhD. Dr Sharma is a medical oncologist and a physician-scientist who specializes in treating gastrointestinal [GI], neuroendocrine, and rare tumors. His research interests include the development of novel early-phase clinical trials and discovery of novel anticancer therapies. He is a world-recognized leader in early-phase drug development and has been instrumental in advancing several drugs from preclinical evaluation through phase 1, 2, and 3, and in immunology. He is also on the scientific advisory board of many biotechnology companies and has an MBA from the University of Massachusetts Amherst. Dr Kundranda is the division chief of medical oncology at Banner MD Anderson Cancer Center, and he will be talking today about immunotherapy—especially in the nonmetastatic GI malignancies and the potential for endoscopic ablation as part of multimodality treatment. Thank you both for joining me today.

Sharma: Thank you for inviting me.

Kachaamy: Dr Sharma, the first question I have for you pertains to where we’re going with early cancer detection. Do you believe that multicancer early detection is becoming a reality? Will that lead to cancer stages shifting, with more patients diagnosed earlier [prompting us] to figure out how to treat them earlier?

Sharma: Yes, thank you for the question. It is really an exciting time in [the realm of] cancer biomarkers, where a lot of effort is being put into detecting cancers early. As you all know, once the cancer is late stage it is really difficult to eradicate [it]. There are many different groups around the world that are working on [developing] more sensitive assays that can detect cancers early. I believe that as these assays improve, [they] will be a real game changer for GI malignancies. The reason I say that is because a lot of these assays in the past that have been used to detect cancers early have been used in slow-growing cancers, like prostate cancers. When you use these assays in those malignancies, you risk this phenomenon called “lead-time bias,” which means that you can detect the cancer early, but it doesn’t really help the patient because detecting the cancer early just simply leads to more unnecessary therapy sometimes because the natural history of those small, slow-growing cancers is so slow. That is not the case with GI cancers. As we all know, most of the GI cancers are aggressive. Pancreatic cancer is the most one of the most aggressive and highly lethal malignancies; colon cancer is the same, and even gallbladder and cholangiocarcinomas are fairly aggressive. As such, it’s a really important [advance] if we could [detect those malignancies] early. In general, philosophically, the lead-time bias would not be a huge concern in my estimation, because the natural history of the disease is so fast. So, that’s one point [I want to make].

The second point on these early detection, multiomic-type assays that are being deployed currently, is that the sensitivity and specificity [of these tests] are not quite there at the moment, but [what we’re seeing is] still pretty darn good. What has happened is that some of the assays that are currently being sold are decent in terms of sensitivity and specificity, but when you want to deploy these assays on a generalized population, you have to have significantly higher sensitivity and specificity and they obviously have to be affordable. So, currently, those 2 things are not quite [where we need them to be], but they’re getting there. There’s a huge amount of effort [that is being made with] this.

The third point I would make is that there has been a lot of recently published research [suggesting] that when you combine these approaches, [so] multiomic-type assays with clinical imaging or other kinds of methodologies, you can increase the sensitivity and specificity to really narrow down that population that you can then help. One example of that would be if you could combine endoscopic observations, for instance, with a multiomic assay—that would improve sensitivity and specificity, so that’s one possibility. The other possibility is combining radiologic [approaches] with [a multiomic] technique. My final thought would be if you could take a high-risk population where you define [what] “high risk” [is] and then use these assays. Then, you would have much more confidence in the moment, and you could narrow [things] down that way. So, those are my thoughts on that and the changing landscape.

Kundranda: You hit on 3 key things [about these assays. You mentioned] making sure [that they are] available to the general public and that it’s not just the lead-time bias that we’re looking at, but that we’re truly making a change in terms of the stage shifting per se. GI malignancies are so heterogeneous. When we think about breast or lung cancers, [they] are heterogeneous in [their] own way, but GI [malignancies] cannot be more heterogeneous than what we deal with in [terms] of management, treatment, and the like.