Irinotecan/Cisplatin Yields Similar Results to Standard of Care in Biliary Tract Cancer

While the randomized phase II Gambit trial (NCT01859728) was negative per study protocol, the combination of irinotecan plus cisplatin appeared active in patients with biliary tract cancer and induced similar results in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with gemcitabine plus cisplatin.

Overall, 47 patients were randomized 1:1 to receive either irinotecan or gemcitabine in combination with cisplatin. The ORR was 35% in the experimental arm versus 31.8% in the gemcitabine arm. The median PFS was 5.3 months versus 7.8 months with the irinotecan versus gemcitabine regimens, and the median OS was 11.9 months and 9.8 months, respectively.

The irinotecan regimen appeared well-tolerated and the adverse events (AEs) were manageable. The AEs were not statistically different between the 2 arms and remained consistent with previous experiences with irinotecan and gemcitabine-based regimens.

Overall, the prognosis of patients with biliary tract cancer who have either metastatic or unresectable disease remains poor. Gemcitabine plus cisplatin is the current standard of care, but these data indicate there may be a role for the combination regimen of irinotecan plus cisplatin in this patient population as well.

In an interview with Targeted Oncology, Luca dos Santos, MD, MsC, medical oncologist, Beneficência Portuguesa in São Paulo, Brazil, discussed the combination of irinotecan plus cisplatin in comparison to gemcitabine and cisplatin as treatment of patients with metastatic or unresectable biliary tract cancer.

TARGETED ONCOLOGY: What was the rationale for conducting this study?

dos Santos: This study was planned in 2012, and at that time, we only had the option in the first-line for gemcitabine plus platinum-based treatment. We were exploring if an increased dose of cisplatin and an exchange of gemcitabine to irinotecan could be useful for the treatment of these patients with advanced biliary tract cancer.

TARGETED ONCOLOGY: How was the study designed?

dos Santos: This is a randomized phase II trial designed to compare if the response rate could be increased using the alternate regimen irinotecan plus cisplatin.

TARGETED ONCOLOGY: What are the results of the study?

dos Santos: This is a negative study per protocol. However, the ORR, PFS, and OS are virtually the same numerically and quite similar when compared to gemcitabine/cisplatin.

The AEs are quite different. Irinotecan plus cisplatin derived more diarrhea for example, and less thrombocytopenia, which is as expected considering the safety profile. Overall, this study, I think, there was that irinotecan plus cisplatin is active and should be tested in more intensified regimens, such as FOLFIRINOX, for advanced biliary tract cancer.

TARGETED ONCOLOGY: Can you describe how the results differed across the different cohorts?

dos Santos: The difference that we saw in AEs was already expected, but in talking about efficacy, the numbers are virtually the same. We are trying to explore if there are some subgroups that could derive more benefit from 1 treatment or another. We are going to do that soon, but I have no clue to tell you about what really happened with the results and why the treatments appeared similar [in the cohorts].

TARGETED ONCOLOGY: Are there any next steps planned?

dos Santos: The next step is to perform molecular analysis of the tumors for the 47 patients and try to figure out what happened and if there is any molecular marker that could derive more benefit with 1 treatment or another.

TARGETED ONCOLOGY: How do you see the treatment landscape for HCC evolving over the next 5 to 10 years?

dos Santos: Nowadays, we put all biliary tract cancer in the same pocket, but we know it's a heterogenous group of diseases. In the near future, we are going to select patients set for molecular markers such as FGFR2, IDH1, and then probably choose the first-line treatment based on these markers.

TARGETED ONCOLOGY: Do you have any other comments on the treatment landscape in your specific field?

dos Santos: I live in Brazil and 1 difficult thing is that we have no support for performing clinical trials and studies in medical oncology. We are trying to get people together, as well as institutions, in a cooperative group in order to make things happen faster.