Ghassan Abou-Alfa, MD, MBA: Let’s move on to a very important component that all of us are involved in as oncologists, which is systemic therapy. I’ll start with Martin, I’ll just put it right out here. How do you approach systemic treatment for patients with cholangiocarcinoma?

Martin Gutierrez, MD: Actually, a cisplatin/gemcitabine regimen as first-line therapy is what I go with, based on the ABC-02 trial data, with improving survival at that point. So that is my first-line. I echo Andrew’s point, when you have an R2 resection, I will treat them the same way. Systemic therapy comes on and then chemotherapy…

Ghassan Abou-Alfa, MD, MBA: Fair enough. You even carry it with the R2, which I totally understand. Andrea, 1 question that we might sometimes face from different doctors is GemOx [gemcitabine, oxaliplatin] versus GemCis [gemcitabine, cisplatin].

Andrea Wang-Gilliam, MD, PhD: Yes. That’s a good question. I generally go by the book and use gemcitabine/cisplatin. I think gemcitabine/oxaliplatin has been used quite often, and if we treat patients sometimes with gemcitabine/oxaliplatin, we do see a good response. However, I think that… the gemcitabine/cisplatin proved to be level 1 evidence by the ABC-02 trial. So, I still use the gemcitabine/cisplatin regimen. However, if patients have kidney problems, sometimes I do use gemcitabine/oxaliplatin.

Ghassan Abou-Alfa, MD, MBA: Fair enough. Definitely there is a little bit of drive sometimes in regard to oxaliplatin, but I agree with Andrea about gemcitabine/cisplatin because where the data came from was a survival improvement close to between 10 and 11 months, which makes a lot of sense. Andrew, 1 of the challenges that we have with the ABC-02 is that the PFS [progression-free survival] is very close to the median survival. There was not much of a difference per se. What are your thoughts on that?

Andrew Zhu, MD, PhD: If you look at the PFS from the ABC-02, it was actually 7 months, and the median survival was 11 months. Clearly the benefit was driven by the first-line regimen because we really do not have second-line treatment at that point. I think the benefit that it derived clearly was mainly because of the first-line regimen. But having said that, the field has been staggering for quite a while since the ABC-02 trial. We actually do not know what additional treatment is better than gemcitabine/cisplatin alone, but also in terms of what we could actually offer the patient if they progress on gemcitabine/cisplatin.

Ghassan Abou-Alfa, MD, MBA: Teresa, your thoughts on ABC-02? Let’s begin with that.

Teresa Macarulla, MD, PhD: I think of course in the moment we do not have any second-line treatment options that are approved, so probably a lot of patients are only treated in the first-line setting with no other options.

Ghassan Abou-Alfa, MD, MBA: Yes.

Teresa Macarulla, MD, PhD: I think it’s a positive trial, and for me it’s my standard. If we have the standard with cisplatin and gemcitabine, I prefer to treat with this combination than with gemcitabine and oxaliplatin. For that, we don’t have the randomized phase III trial.

Ghassan Abou-Alfa, MD, MBA: Along that line, I have a question for you, and probably you are the right person to ask because you practice here in Europe. The ABC-02 trial limited the treatment to 6 months. In the United States, we carry on with treatment until progression or intolerance. Your thoughts on that? How do you practice? How do you read the data?

Teresa Macarulla, MD, PhD: I don’t like to stop the treatment.

Ghassan Abou-Alfa, MD, MBA: You don’t? OK.

Teresa Macarulla, MD, PhD: No. I try to stop the cisplatin after 6 months normally due to toxicity, but I continue with gemcitabine as maintenance monotherapy. But there are a lot of physicians here in Europe that stop after 6 months. It’s very common.

Ghassan Abou-Alfa, MD, MBA: Sure. Quite fascinating. We’re hearing about gemcitabine/cisplatin, which was built on the ABC-01 trial, and the data of this was moved to ABC-02, and ultimately, we had an improvement in survival of about 11 months versus 8 months for the gemcitabine/cisplatin versus gemcitabine. We give a lot of credit to the UK group in regard to that data. That became standard of care as we heard from all of us. There are 2 challenges that have come with that study. Number 1, understandably, the progression-free survival was rather high, and we all know that progression-free survival is dependent on a very important variable: When do you look at it? Also, if you do a CT [computed tomography] scan every week, you’ll be able to get a progression-free survival that’s more specific, and maybe would be determined by when you do those scans. On the other hand, if you do the scans less often, you can only register that progression-free survival whenever it happens.

Regarding the ABC-02 trial, the frequency of scans was less than we do in the United States. That’s why probably the progression-free survival was more than what could have been expected. This is something that can be revisited. Why do we bring up this information? This is because, of course, we need references for those studies, so we can depend on them for whatever future studies we’re going to do.

The other point that was brought up is exactly what Dr Macarulla was talking about, which is, do you stop after 6 months? There is a certain approach in the United Kingdom that after 6 months of therapy, that’s it, we can stop the treatment because we try to measure it from a different perspective—being, of course, benefitting the disease and make sure it responds. Number 2, is preventing any adverse events and the functionality of the patient per se.

In the United States, and as we just heard, even for certain physicians and colleagues of ours in Europe, there’s probably a carry on in the therapy until progression or until there is an adverse event that might limit treatment. For that reason, yes, as we heard from Dr Macarulla, there could be some practicality where we might stop the cisplatin first and continue on the gemcitabine. By the way, there is a theory that maybe a certain remembrance effect for the cisplatin can carry on after the cisplatin is discontinued while the gemcitabine is on. So, there could be variation on how we’re applying it.

Transcript Edited for Clarity