Milind Javle, MD: Before we get there, Anjana, you mentioned that you’re seeing more patients in your clinic now, and that’s also my experience. We’re seeing a lot more biliary cancer, and I’m amazed that some fellows come to my clinic and say they want to specialize in biliary tract cancer [BTC], which nobody ever did in the past. What has led to this? Do you think there’s an increase? Is there a role in geography, ethnicity? Could you also highlight some risk factors that you alluded to earlier?

Anjana Pillai, MD: Absolutely. I agree. We’re all seeing more. Of course, you had a recent paper, which I tweeted about, in The Oncologist that showed that incidence updated to your database that’s reflective of all our practices. The study that I like to quote was from the Journal of Hepatology a few years back, but it showed that only 30% of these tumors have identifiable risk factors. In the United States, we don’t see liver flukes. When I educate my patients, I talk about stones and cortical cysts being a risk factor, but that’s a minority of the patients that I see with biliary cancer.

Of course, there’s underlying cirrhosis and hepatitis B and C, but we don’t see tons of hepatitis B. Hepatitis C, with new direct antiviral therapies the last 8 years, has also decreased. The number of patients I see often have de novo with no underlying liver disease and no identifiable risk factors. Of course, we always think about obesity, metabolic syndrome, alcohol, and smoking, but we haven’t identified 1 true risk factor for which we can truly say, “If you have this and this without underlying liver disease, then you’re at increased risk.” Then, there’s PSC [primary sclerosing cholangitis]. Historically, that’s always been the link with PSC, UC [ulcerative colitis], and cholangitis. Almost 50%, maybe 70%, of our practice has no underlying liver disease, which makes it challenging how to identify these patients early, risk-stratify them, or screen for them.

Milind Javle, MD: Anjana, you raise an important point about PSC. Clearly, there’s excitement in immunotherapy, in BTC, or in all cancers, but we’re going to see these patients who have PSC, ulcerative colitis, and Crohn disease, and then we’re going to talk about immunotherapy and checkpoint inhibitors. We’re certainly going to send these patients in your direction for hepatology guidance. What plans do you have in mind?

Anjana Pillai, MD: It’s a difficult question because most of these autoimmune-type patients were typically excluded from these clinical trials, so it’s not a patient population that we have tons of data with. These checkpoint inhibitors can also mimic. Very rarely do you get these immune-related events where they can mimic a PSC or IgG for cholangitis. PSC is a different entity than true autoimmune hepatitis. In that sense, there’s not that fear of a flare or that significant decompensation. Depending on how advanced the PSC is and their Child-Pugh score, as a group we’d determine chemotherapy, including immunotherapy, but my sense is that the well-compensated patient with PSC should do OK with immunotherapy.

Milind Javle, MD: Wonderful. I’ve treated some patients. I’m going to jump to Mark. Mark, you’re a resident I/O expert. How are you considering treating these patients who have an underlying autoimmune disease, maybe PSC, maybe ulcerative colitis? I’ve had patients with other diseases, underlying multiple sclerosis, ankylosing spondylitis—that sort of thing.

Mark Yarchoan, MD: This is an area where it would be great to have more data. In general, we’re usually willing to offer immunotherapy for patients who have no severe underlying autoimmune disease and who aren’t on active immunosuppression. In every case, you must weigh the risks and benefits. We’ll be talking about the new data for immunotherapy in biliary tract cancers. Clearly, this is an important development, but the absolute benefit in terms of median survival is modest. There’s a risk of exacerbating underlying autoimmune disease. My willingness to add durvalumab in frontline treatment for PSC is a discussion, but it’s not something I would offer to everybody.

Transcript edited for clarity.