Treating Metastatic Cholangiocarcinoma
An overview of the standard of care for patients with metastatic cholangiocarcinoma, and the significance of conducting clinical trials that increase the number and types of therapies available to patients with fewer adverse events and better results.
Afsaneh Barzi, MD, PhD: For advanced metastatic cholangiocarcinoma, the standard of care is gemcitabine and cisplatin based on the ABC-02 trial, which was published almost 12 or 13 years ago. There are 2 trials that are worth mentioning. One is the SWOG-S1815 trial and the PI [principal investigator] is [Rachna] Shroff, [MD] . This looked at triplet chemotherapies, where they added Abraxane [nab-paclitaxel] to gemcitabine-cisplatin. Everybody’s eagerly waiting for the results of the trial. On October 25th [2021] there was a press release from AstraZeneca reporting that the TOPAZ trial, which looked at gemcitabine-cisplatin versus gemcitabine-cisplatin in combination with durvalumab, had met its primary end point for improvement in overall survival. It was a positive trial. Although I haven’t seen any of the results, I think it is very encouraging that maybe immunotherapy is going to be a therapeutic option for the frontline setting of patients with cholangiocarcinoma. One thing that we must keep in mind is that in many of these frontline therapies, whether we look at ABC-02 or TOPAZ, or many other trials, there is a mix of cholangiocarcinoma and gall bladder cancer. In other words, these are trials for biliary tract cancer, and therefore, gall bladder cancer is also included in the trial population. It’s important to know those caveats and minor differences between these trials. There’s another trial that I am guessing we should see the results for some time very soon. That’s KEYNOTE-966, which looked at the combination of pembrolizumab with gemcitabine and cisplatin. I am guessing if the…trial was positive, that this one hopefully will be positive too, so the results of that one are eagerly awaited.
The gentleman in this case received an excellent therapy. I think gemcitabine-cisplatin is the upfront therapy in this patient population. This patient had a bilirubin level under 2 [mg/dL]; I know we are cautious about using gemcitabine in patients with high bilirubin. He did have a performance status of 1, all of which are meeting the requirement for offering this therapy. It’s not the easiest therapy; it does have adverse effects like any other chemotherapy that we offer. I think the oncologist is doing a fabulous job monitoring the patient and adjusting based on the toxicities that were reported, which included fatigue and neutropenia. I think the treatment was very appropriate. The data I shared for gemcitabine-cisplatin and durvalumab are very new. It wasn’t available at the time this patient was diagnosed, and it’s not a standard of care as we are speaking. We’re just seeing a glimpse into the data, however, yes, this gentleman got very appropriate therapy.
I think clinical trials are important in every oncological disease we look at. For cholangiocarcinoma, the importance of clinical trials is magnified…because it is a rare disease. We should think about how we all have to come together, from the oncology community to the patients, to actually find the best treatment for these patients. We do not have a lot of specimens to test, with a limited number of patients in a rare disease, and therefore for those we have, we have to make sure we are channeling them to the appropriate clinical trials. As I mentioned earlier, about 15% to 20% of cholangiocarcinoma cases have targets. Therefore, there are many ongoing trials exploring these targets in this patient population. An example is that infigratinib, which now has an FDA approval in subsequent lines of therapy in patients with an FGFR alteration, has an ongoing trial in the frontline setting with the control arm of gemcitabine-cisplatin. It is looking to see if this would be an opportunity to look at the chemotherapy-free or targeted therapy-only option in these patients with FGFR alterations. It’s important to identify these patients and refer them for trials. Similarly, futibatinib, which is another drug targeting FGFR alterations, is looking in the frontline setting for patients with FGFR2 alterations. Again, it’s looking for a chemotherapy-free option, at least for a select patient population.
There are numerous ongoing trials in the second and subsequent lines of therapy; we must truly think about these trials and channel our patients appropriately. Going back to what I mentioned earlier, timely molecular testing is our key for identification of patients with targetable alterations, and referral of these patients to the appropriate trials.
Transcript edited for clarity.
Case: A 75-Year-Old Man with Metastatic Cholangiocarcinoma
May 2021
Initial presentation
- A 75-year-old man presents with abdominal pain and weight loss.
Clinical workup
- History of hepatitis B infection more than 10 years ago and hypertension which is controlled with medication
- Blood work reveals serum levels of CA 19-9 (1200 U/ml), bilirubin 1.5 mg/dL, ALT 250 U/L, AST 95 U/L
- MRI imaging shows multiple liver masses
- Histopathological examination identifies adenocarcinoma with primarily mucin-producing glands
- Patient is identified to have intrahepatic cholangiocarcinoma (iCCA).
- CBC is unremarkable (absolute neutrophil count 3,500/mm3, platelets 300,000/ml, hemoglobin 10.1 g/dL)
- ECOG PS is 1 and the patient is in good health.
- Patient is referred to oncologists for next steps and is started on treatment with gemcitabine and cisplatin in June 2021.
Sept. 2021
- Patient is experiencing grade 2-3 neutropenia and fatigue and the oncologist has adjusted the dose to reduce toxicities with chemotherapy.
