The Role of Targeted Therapies in Advanced Cholangiocarcinoma - Episode 5

CCA Important Developments and Practical Advice

Targeted Oncology

Rachna Shroff, MD: It is such an exciting space in cholangiocarcinoma in terms of drug development and focusing on novel therapeutics for these patients. It’s hard to summarize that. Obviously, everybody, anybody who treats the disease, as well as the patients, want immunotherapy to work in cholangiocarcinoma. Initial studies have been disappointing in terms of single-agent checkpoint inhibition with the KEYNOTE data that came out with pembrolizumab, for instance. This year at ASCO [the American Society for Clinical Oncology annual meeting], for instance, we’re seeing signalssuggesting that immunotherapy does have a role. There are the data out of Korea that are, again, looking at checkpoint inhibition. Granted, we know that’s a primarily Asian patient population and that is probably biologically a somewhat different population than say the patients we treat in the United States.

There were the data looking at nivolumab and ipilimumab, for instance. While the data were a little disappointing out of the University of Michigan, again it does suggest that we can and should be thinking about immunotherapy. The single-agent data with nivolumab out of Moffitt [Cancer Center], which were published recently, definitely piques everyone’s curiosity and raises eyebrows because it’s a higher response rate than we had seen, for instance, in other single-agent checkpoint studies. That being said, that was an investigator-assessed response as opposed to a centrally reviewed radiographic response.

The point is I think that there is a lot of excitement and enthusiasm to figure out how to make immunotherapy work, and I think all eyes are on the frontline studies. There’s a gemcitabine/cisplatin with nivolumab, there’s a gemcitabine/cisplatin with pembrolizumab, durvalumab. There’s a lot of interest. We’re keenly awaiting those data to see if perhaps there is a synergy when you use cytotoxic chemotherapy with checkpoint inhibitors since we’re not 100% sure that checkpoint inhibitors alone can work.

In terms of other areas of interest, I think of course as we use targeted therapies, we are seeing resistance emerge, and trying to understand how to approach FGFR2 [fibroblast growth factor receptor 2] resistance, for instance, given that we have so many drugs available, can we treat these patients sequentially? Are there mutations that we can follow on ctDNA [circulating tumor DNA], for instance, that could help guide that therapy? That’s an area of great interest to us as we’re treating these patients in the clinic and as these drugs become available. The infigratinib study that’s ongoing for patients who already received prior FGFR therapy is a really important piece to that puzzle.

I am a firm believer that cytotoxic chemotherapy is down but not out, if you want to call it that. My hope is that we can build on gemcitabine and cisplatin in the frontline setting or FOLFOX [folinic acid, fluorouracil, oxaliplatin] in the second-line setting. There are a lot of frontline studies right now that are looking at nucleoside analogues, like the NuCana [Plc] study, which is the nucleoside analogue similar to gemcitabine with cisplatin. There’s SWOG 1815, which is a randomized study that I am very interested in seeing the results on since I’m the national principal investigator, but it’s gemcitabine and cisplatin versus gemcitabine, cisplatin, and nab-paclitaxel, so a triplet chemotherapy regimen to see if we can augment response and survival in newly diagnosed patients. I think there’s a lot of work going on in a lot of different spaces, and I don’t doubt we’re going to have more drugs for our patients soon.

My advice to community oncologists when it comes to using targeted therapy in cholangiocarcinoma is first, there’s a role. I think educating everyone, not just community oncologists, but everyone about the role that targeted therapy can and should be playing in cholangiocarcinoma is really important. Number 1, is the importance of doing molecular profiling with next-generation sequencing on patients and doing that efficiently and right at the time of diagnosis, so that you could integrate what you learn from those reports into your algorithm for treating these patients.

The other advice I would say is that back when I first started treating this disease, it was slim pickings in terms of clinical trials being available for our patients. Now there are so many trials out there, and if a community oncologist doesn’t have a great idea after gemcitabine/cisplatin or even doesn’t have a great idea in a newly diagnosed patient, please refer them to an academic tertiary cancer center that has a robust clinical trial portfolio because we are absolutely moving the needle forward on these patients, and we’re doing our trials. My advice would be to collaborate with the experts in the field and help us continue to make progress.

Transcript edited for clarity.