At the SIR 2024 Annual Meeting, Qian (Clark) Yu, MD, University of Chicago, Illinois, shared results from a retrospective review, evaluating the combination of transarterial radioembolization (TARE) with systemic capecitabine for patients with unresectable cholangiocarcinoma. The median overall survival for this treatment was 22 months.

Dr Yu shares the rationale for combining local therapies with systemic therapies for cholangiocarcinoma, why some medical oncologists are hesitant to consider local therapies for this patient population, and the importance of multicenter collaboration for trials in interventional oncology.

Transcript:

IO Learning: Please give a brief overview of the background and the rationale for this study.

Qian (Clark) Yu, MD: At our institution, we have really good cholangiocarcinoma program. We're one of the few institutions that offers liver transplants and the live donor liver transplant for patients with the intrahepatic cholangiocarcinoma. We have a lot of patient referrals from medical oncologists, hepatologists, surgical oncologists for treatment of resectable cholangiocarcinoma carcinoma. Typically, this disease is pretty aggressive. Patients are usually diagnosed very late, and the majority are not resectable at time of diagnosis.

If there's no resection, the question is how do we treat those patients? Current standard of care is systemic therapy. There was a trial called ABC02 trial, published in 2010 in the New England Journal of Medicine. It made the combination of gemcitabine and cisplatin the standard of care for unresectable disease.

Then, Y90 came out, and people started to evaluate whether Y90 can be helpful in this scenario. First of all, the studies, including a lot of the studies that we published, show that Y90 can achieve a high rate of pathological necrosis for cholangiocarcinoma on pathology. It has really good tumor control. We just published data on using Y90 to promote contralateral hypertrophy of liver to prepare patients for surgery. Initially you have large tumor burden that cannot get surgery. We use Y90 to shrink the tumor to bridge to provide a local control and also promotes contralateral hypertrophy, so patients can become better surgery candidates. This is why we're evaluating Y90 for this patient population.

IO Learning: What were the methods of this study?

Dr Yu: Cholangiocarcinoma, it's different from HCC [hepatocellular carcinoma]. In the US when we find HCC, a lot of patients are in early stages, we can provide definitive treatment.

But for cholangiocarcinoma, patients are usually diagnosed late and sometimes upon diagnosis, we don't know whether they have a metastasis. I did a surgery internship and there were scenarios where we brought the patient for liver resection, we thought it's a local disease, but during surgery, we found a microscopic, very small satellite mass.

Y90 can also be a good way to test the biological aggressiveness. You know, when patients come in with this aggressive disease, we don't know whether it's local or already has metastases. We give Y90 and we also combine them with systemic treatment in case they have a metastasis. We have to get this kind of small tumors as well. We give Y90 plus systemic treatment and then do reimaging in 3 months to see whether the disease is stable or not. If a patient has responded and that's good, we continue our standard treatment, hoping to bridge this patient to surgery. And in our institution, if a patient is stable for 9 months, we offer liver transplant.

IO Learning: What were the results of the study?

Dr Yu: Currently, based on this project, we combine with capecitabine. The reason we combine with capecitabine, it's a radiation therapy sensitizer. It has been used in combination with a radiotherapy in other cancers, such as pancreatic cancer, colorectal cancer and breast cancer. With this regimen, our preliminary data shows the overall survival of 22 months. And this is comparable with the MISPHEC trial, a multicenter prospective, phase 2 trial published on JAMA Oncology. It was done in Europe. They use first-line Y90 plus gemcitabine and cisplatin for unresectable cholangiocarcinoma. They also reported a median overall survival of 22 months.

It's comparing apples and oranges, but it showed that there's potential benefit with such a combination regimen.

IO Learning: What is the significance of these results?

Dr Yu: There’s a fierce debate between different specialties. Some medical oncologists don't trust locoregional therapy for cholangiocarcinoma because they feel there's a strong systemic component, which would we agree. And in many institutions, human border when interventional radiologists offer, let's try Y90 for cholangiocarcinoma, they say, no, there's not enough data. And we have a lot of systemic therapies under development, we should test this therapy out instead.

Our approach is to combine locoregional, such as Y90, and a systemic therapy. This study provides evidence for other institutions, when, during a tumor board, the oncology says, “Oh, no, we're going to go systemic only.” With this data, we can say, it doesn't hurt to combine with locoregional therapy, such a Y90. If you want to try to offer systemic therapy, that's okay, but let's combine with Y90. It can provide additional local tumor control and can even, like I said, promote functional liver reserve to bridge the patient to surgery. That's something that a systemic therapy is not able to do.

IO Learning: Is there anything else you’d like to highlight about this research?

Dr Yu: I gave another presentation on ablation, which is another local regional therapy for cholangiocarcinoma, during the plenary session at SIR. One thing I really want to highlight is that as an interventional radiologist, the food chain referral is not upfront. Cholangiocarcinoma is a very rare cancer and not many institutions are dealing with this kind of cancer. And currently, there are a lot of systemic treatments available. The medical oncologists are getting more trials, more data. It's even harder for us to get enough data, homogeneous data, to show that locoregional therapies work.

I feel it's very important for the interventional radiology community to collaborate, to prepare multicenter trials in this setting, to evaluate Y90 in combination with different systemic regimen at different stages for different purposes to get more high-level quality evidence to to support our approaches during tumor boards. I think multicenter collaboration is very important in this setting.

Sources:

Yu Q, Wang Y, Hwang G, et al. Safety of transarterial radioembolization plus adjuvant systemic capecitabine for treatment of unresectable biliary tract cancer. Presented at Society for Interventional Radiology Annual Meeting. March 23-28, 2024; Salt Lake City, UT

Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2020;362:1272-1281. doi:10.1056/NEJM0908721

Edeline J, Touchefeu Y, Guiu B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: A phase 2 clinical trial. JAMA Oncol. 2020;6(1):51-59. doi: 10.1001/jamaoncol.2019.3702