Sequencing Therapy With Novel Agents in Metastatic Cholangiocarcinoma
Clinical pearls regarding molecular testing and treatment selection in metastatic cholangiocarcinoma.
Afsaneh Barzi, MD, PhD: There are good chemotherapy combinations in this patient population. We talked about FOLFOX [folinic acid, fluorouracil, oxaliplatin] based on the ABC-06 trial, and we talked about 5-FU [fluorouracil] and Onivyde [liposomal irinotecan] based on the NIFTY trial. There are targeted therapies for patients we are identifying, and in those who are MSI [microsatellite instability]-high, pembrolizumab remains a recommended second-line therapy in this patient population. Outside of that, although there are some smaller studies and a recommendation by NCCN [National Comprehensive Cancer Network] to consider immunotherapy in subsequent lines of therapy, I would say I don’t have any high-quality data to strongly recommend immunotherapy. I think we have very good chemotherapy options that have shown efficacy in trials and very good targeted therapy options, if you’re thinking about immunotherapy, we should really see trials that are evaluating immunotherapy in second and subsequent lines of therapy. Additionally, if immunotherapy makes its way to the frontline setting, and if patients are all potentially exposed to immunotherapy in the frontline setting, the role of this treatment in subsequent lines of therapy is going to go away. Immunotherapy in the second and subsequent lines of therapy for cholangiocarcinoma is not high on my list for most patients.
I would say cholangiocarcinoma is a mysterious disease. It is important to make sure our patients have cholangiocarcinoma. Patients present with liver metastatic disease, but a patient with colon cancer would present liver metastatic disease, so appropriate work-up to make sure this is truly cholangiocarcinoma is important. If a patient hasn’t had a colonoscopy, considering colonoscopy and EGD [esophagogastroduodenoscopy] is important. There are some data that cholangiocarcinoma, and especially intrahepatic cholangiocarcinoma incidence, is rising, but it is believed that the rise is actually based on a better classification of tumors of unknown primary to cholangiocarcinoma. My general advice is if you see somebody with liver lesions, and you do a biopsy and it comes back adenocarcinoma, hepatobiliary primary, that is not necessarily a pancreatic cancer if you don’t see anything in the pancreas. That’s an important consideration because for the pancreas, FOLFIRINOX [folinic acid, fluorouracil, irinotecan, oxaliplatin] is a standard therapy. However, in a recently published study, FOLFIRINOX is actually not a good therapy for cholangiocarcinoma. We must be careful to label these patient cases appropriately and make sure we rule out common diseases such as colon cancer. And again, for a biopsy of the liver that reads as hepatobiliary malignancy, if you don’t really see any pancreatic cancer or pancreatic lesions, think about cholangiocarcinoma. The treatment paradigms are very different, and it’s important to think about that.
Next, I would say don’t forget the molecular testing in this disease. This disease now has targeted therapies that are FDA approved. There are also many trials that are ongoing, targeted therapies that have good data behind them although they don’t have FDA approval, and those treatments are listed in the NCCN guidelines. I think as oncologists, our most important job is to label these cases appropriately, do not mislabel a patient with cholangiocarcinoma as having pancreatic cancer, and do not label them as cancer of unknown primary. It is our responsibility to label them appropriately, and it is on us to do appropriate and timely testing for identification of biomarkers. It’s on us to appropriately transition them from one line of therapy to another, and to not miss the opportunity for the patient to get exposed to an effective therapy that can control their disease for a long time.
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.
