Ghassan Abou-Alfa, MD, MBA: It will be nice to carry on and go back to what Andrew started the discussion on, which is what do we do with a patient with cholangiocarcinoma? We’ll start again with Martin. The disease is limited to the liver, is away from blood vessels, with no satellite lesions, and there is great functionality. What do you do with this 1?

Martin Gutierrez, MD: As Andrew said previously, surgery is the key for sure, so that’s the straight answer for the cholangiocarcinoma.

Ghassan Abou-Alfa, MD, MBA: I totally agree. We’ll make it a little more difficult for our friend. Andrew, what would you do if 2 satellite lesions are hanging around in the periphery?

Andrew Zhu, MD, PhD: If the surgeons say they can cut it and cut it completely, then I would do that. What we define by complete is really R0 resection. I think surgical resection should be taken. We should definitely give the patients the best chance to cure. I think the only curative modality is surgical resection. For that reason, even you have satellite nodules, if it can be rendered resection, I would still proceed.

Ghassan Abou-Alfa, MD, MBA: Understandable. If anything, resectability remains the only curative approach, and there could be some debate about having satellite lesions in regard to resectable by definition exactly as Dr Zhu mentioned. But at the same time, what does it mean? There have been some data that an approach of systemic therapy would be the applicable one per se. Regardless, let’s just carry on with the surgery part, and let’s talk about adjuvant therapy. Teresa, do you give any adjuvant therapy for cholangiocarcinoma?

Teresa Macarulla, MD, PhD: Yes. We know that the recurrence of the disease is so high that I try to give adjuvant treatment if I can to all the patients after surgery. The problem is, which is the best treatment? It’s not so easy because we have the capecitabine trial, the only positive 1 we can discuss. But I am not so convinced with this regimen.

Ghassan Abou-Alfa, MD, MBA: You’re referring to the BILCAP study.

Teresa Macarulla, MD, PhD: Yeah.

Ghassan Abou-Alfa, MD, MBA: OK, so what is not convincing you?

Teresa Macarulla, MD, PhD: It is because in fact it’s a negative trial. If you see the primary endpoint, then this prespecifies the sensitivity analysis, and then the overall survival becomes positive. I like to treat the patients with a more convenient strategy, but for now we have only this. So I treat my patients with capecitabine, and if a patient is within advanced disease, meaning more lymph nodes affected, probably I treat the patient with gemcitabine-based chemotherapy with no randomized data.

Ghassan Abou-Alfa, MD, MBA: Fair enough. Andrea, any thoughts on the BILCAP study?

Andrea Wang-Gillam, MD, PhD: I agree. It’s tough. When you think about disease that’s so aggressive and has a high risk of recurrence, you want to give more aggressive chemotherapy. Capecitabine does not seem to be that aggressive in oncologists’ eyes. Even the study is positive… You wonder if you should do more in this disease. There have been some small studies with a combination treatment, a SWOG trial that also showed interesting data. I think the question is still, is this enough? What else can you do in those patients?

Ghassan Abou-Alfa, MD, MBA: Sure. I would like to dissect the BILCAP study a little bit further. If anything, Andrew, if I recall correctly, the median recurrence-free survival was about 24 months with the capecitabine and about 17-plus months with observation.

Andrew Zhu, MD, PhD: Correct.

Ghassan Abou-Alfa, MD, MBA: Your thoughts on that?

Andrew Zhu, MD, PhD: As Teresa mentioned, if you look at the intent-to-treat population, clearly the OS [overall survival] did not actually meet the primary endpoint of improved overall survival. I think the P value was like 0.09. Having said that, if you look at the absolute value with the control arm versus the treatment arm, you have a very significant delta. The treatment arm actually survived, and the overall survival was actually in the range of 51 months, in contrast with something like 36 months. I think the delta is definitely more important.

I think what’s really complicated in this particular study is the so-called prespecified sensitivity analysis protocol, which really makes it very difficult for general oncologists to appreciate. At the end of the day, do you look at the intent-to-treat primary endpoint and declare this 1 is a true negative? Or do you say maybe we should actually count every single variable, so we can consider this a potential good benefit to our patients?

At the end of the day, you have a population that has very high risk for recurrence. You know they will do poorly without treatment, and this is probably still the best of the data. More aggressive regimens have been tested. The GemOx [gemcitabine, oxaliplatin] has been tested and came out negative. In that setting, at this stage, if I have to consider a patient with adjuvant treatment, if I truly evaluate the patient with R0 resection, based on the best evidence, I probably would go with capecitabine right now, based on the BILCAP data. But if a patient has R1 or R2 resection, I think the decision is easy. I have to treat this 1 just basically still as a systemic situation. I’ll use GEM [gemcitabine]—CIS [cisplatin] as my first-line therapy.

Ghassan Abou-Alfa, MD, MBA: That’s quite fascinating. If anything, we’re hearing that on 1 hand, there have been a lot of suggestions that a certain form of adjuvant therapy would be valid and applicable. We heard about BILCAP data, even though I totally agree with Andrew that this data had some nuances. We’re not necessarily going to understand fully how the interpretation of the outcomes was there. In regard to other efforts that were then regarding chemotherapy, the 1 that was referred to again by Dr Zhu is the 1 of Dr Julien Edeline in regard to the GemOx, which was negative. I have to say that certain perplexity was brought up in regard to the use of adjuvant therapy for biliary cancer. Of that we are using it almost probably by default, rather than because we really have a strong necessity that we can argue or support our decision to treat with adjuvant chemotherapy.

Transcript Edited for Clarity