Biliary Tract Cancers: Standard of Care Treatment Strategies

EP: 1.Overview of Biliary Tract Cancers and Diagnosis

EP: 2.What is the Role of Biomarker Testing in Biliary Tract Cancers?

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EP: 3.Biliary Tract Cancers: Standard of Care Treatment Strategies

EP: 4.Chemoimmunotherapy in Biliary Tract Cancers: Data From TOPAZ-1

EP: 5.Other Clinical Trials With Chemoimmunotherapy in Biliary Tract Cancers

EP: 6.The Evolving Treatment Landscape of Biliary Tract Cancers

Transcript:
Laura W. Goff, MD: Another change that’s happening rapidly is the standard of care for patients with advanced biliary tract cancer. How has the approval of TOPAZ-1 changed the treatment landscape for cholangiocarcinoma?

Milind Javle, MD: You and I have been on this journey for over a decade, and [the advancements have been] staggering. In the last 3 years, we’ve had 5 approvals. This year we might get another 1 or 2. It’s a fabulous journey. For a decade we had nothing in the first-line setting except gemcitabine-cisplatin. We used gemcitabine-cisplatin for everybody. When we did a community-based survey of treatments—my fellow Dr [Madhu] Elluri did that—15% never got treated because they had liver function testing, poor performance status [PS], kidney problems, or some issue that prevents any therapy. Of the 85% [of patients] who get treated, we typically treat them with gemcitabine-cisplatin. If the PS is ECOG 2, then we treat with single-agent gemcitabine. That has dramatically changed over the last year. I’ve been using gemcitabine-cisplatin-durvalumab routinely for all patients in the first-line setting unless they have some contraindications. What about you, Laura? Is that what you’re doing in your practice?

Laura W. Goff, MD: Yes, we’ve adopted gemcitabine-cisplatin-durvalumab as our standard. The recent data presented with a similarly designed trial of gemcitabine-cisplatin-pembrolizumab has strengthened our belief that chemoimmunotherapy is, without contraindications, our standard first-line approach.

Milind Javle, MD: It’s quite impressive. I was somewhat nihilistic about the role of immunotherapy in this setting because prior trials indicated a response rate of 5% to 6% in unselected patients with pembrolizumab. Clearly, there’s an impact. This has made it into the NCCN [National Comprehensive Cancer Network] Guidelines. I believe it was category 2B, [but now it’s] category 1. Any thoughts?

Laura W. Goff, MD: It’s an emphasis on the belief that this is a real benefit. It was adopted relatively quickly, despite that change, but it lends additional credence to the regimen. The other thing that’s interesting is that part of the reason the recommendation changed is that the benefit is seen somewhat later. Immunotherapy takes a little while to kick in. When the data were originally presented, I had some concerns about the overlap or closeness of the curves early on. But the real benefit of immunotherapy is seen after what we usually think of as the up-front 6-month benefit of chemotherapy. Over time, as we’re getting a little more maturation of our experience and the data, we’ve grown more confident in the use of this regimen.

Milind Javle, MD: I agree. I want to also mention that the TOPAZ-1 trial shows a median overall survival improvement from 11 to 12.8 months with the addition of durvalumab compared with chemotherapy alone. It underscores the benefit we see. I’ve been very impressed with the adverse effect profile and the tail on the curve, which shows a 2-year survival of about 24%. What’s your impression of patient tolerance to this regimen? Do you notice any added adverse effects when we add a third agent?

Laura W. Goff, MD: My clinical experience has been quite good with the triplet [therapy]. Obviously, there are risks for immune-related adverse effects. We’ve been doing it for only a year and a half, but it has been tolerated quite well. Single-agent immunotherapy—with durvalumab as the only immunotherapy agent we’re combining with gemcitabine-cisplatin—seems to be well tolerated. I’ve worked with the fellows for years, and I always emphasize that the biliary cancer cisplatin dose is lower than a lung cancer dose. You don’t want to be giving lung cancer doses of cisplatin. The gemcitabine-cisplatin regimen as a backbone is well tolerated by itself. This seems to combine well with durvalumab. Most of my patients are able to tolerate this, even those who are relatively older or have some level of comorbidity.

Transcript edited for clarity.