The Evolving Treatment Landscape of Biliary Tract Cancers

Transcript:

Milind Javle, MD: Laura, the first line is a very exciting area for biliary tract cancer. But there’s been a lot of activity and movement in NCCN [National Comprehensive Cancer Network] Guidelines for second- and subsequent-line therapies. Could you comment on the recent guideline updates and approvals besides durvalumab?

Laura W. Goff, MD: A lot of regimens have demonstrated activity. For a long time, we didn’t know if there was even value in giving second-line therapy to the existing therapies that we had. First, it’s very important to evaluate if a patient tumor harbors an actual alteration. At this point, those are top tier in terms of what we want to look at. If there’s an FGFR alteration, FGFR fusion specifically, we want to treat with the FGFR-targeting agents such as pemigatinib or futibatinib. If there’s an IDH1 mutation, we’d also target that.

Less well known among community oncologists is that we’ve shown the value of using chemotherapy in the space. For a long time, there was a question of whether chemotherapy had some benefit. [There was a] very modest benefit, but shown vs active symptom control was the role of FOLFOX [5-fluorouracil, leucovorin, oxaliplatin]. The role of 5-FU [5-fluorouracil] and liposomal irinotecan was compared with 5-FU alone as an active control. [Patients] showed benefit from this 5-FU and liposomal irinotecan combination.

We have a lot more choices than we had 5 years ago. Coming back to the point you made earlier that many patients still aren’t receiving therapy. There are times when I’m still reminding colleagues that patients benefit and to consider treatment, rather than the nihilistic view that nothing works.

Milind, tell me a little more about out-of-the-box or emerging therapies you’ve been exploring for patients.

Milind Javle, MD: Laura, we have a multidisciplinary meeting at [The University of Texas] MD Anderson [Cancer Center] every Tuesday. I’m amazed by the number of options patients have. You and I spent a lot of time talking about targeted therapies, immunotherapies, and so on, but the treatments for these cancers is truly multidisciplinary. We’re learning how to use these therapies within the context of surgery. Should we consider neoadjuvant or adjuvant [therapy]? How do you incorporate radioembolization for consolidation?

This is an evolving field. We have to learn to integrate these therapies in a multimodal way to make a true impact. It takes a village, not just medical oncologists but a lot of specialists. These patients are best managed in the multidisciplinary setting at high-volume centers such as yours, mine, and others.

Laura W. Goff, MD: That’s critical.

There are a lot of unmet needs. Tell us a little about what you’re excited about or the key unmet needs in the treatment of advanced biliary tract cancers.

Milind Javle, MD: There’s been a lot of excitement with the therapies you described: immunotherapy, targeted therapy. The benefit is somewhat incremental and often not long lasting. The proportion of patients who derive benefit is limited. For instance, you and I are very excited with the 24%, 2-year survival with TOPAZ-1, but I described that to a patient. [They said] “This is what you call success?”

We have to identify the patients who benefit and perhaps exclude those who don’t. What more can we do in the space? How can we make tumors more immunogenic? There’s a lot of activity in that space, whether combining targeted therapy with immunotherapy drugs. There’s activity and interest in modifying the human microbiome to make the tumors more immunogenic. Perhaps combining checkpoint inhibitors [will have benefit]. For instance, in liver cancer, the additional CTLA4 to durvalumab had a benefit. Are there other checkpoint combinations that might have greater value?

As we learn more about the diseases, we’ll definitely identify more subtypes. Besides the FGFR and IDH1, this year we’ll hear a lot about [INAUDIBLE], for instance. But there are more biomarkers that we’ll investigate. I’m also interested in looking at research pertaining to novel checkpoint inhibitors, novel checkpoint combinations, and ways to modify the tumor microenvironment…. I’m quite amazed that there’s so much activity [in this disease]. I’m looking forward to…the next 5 years, or even sooner, when you’re going to see great progress.

Laura W. Goff, MD: I agree.

Transcript edited for clarity.