IDH Inhibition in Metastatic Cholangiocarcinoma
Implications for treating select patients with metastatic cholangiocarcinoma with ivosidenib as second-line therapy.
Afsaneh Barzi, MD, PhD: Ivosidenib was also FDA approved this year for patients with cholangiocarcinoma and an IDH mutation. There was a randomized study looking at ivosidenib versus placebo, allowing the patients on placebo to be switched over to ivosidenib. It showed an improvement in the PFS [progression-free survival], which was the basis for FDA approval. In the control arm, the PFS was 1.4 months, and in the ivosidenib arm the PFS was 2.7 months with a hazard ratio of 0.37, and a significant P value. Although numerically it’s a small improvement, it is a very respectable hazard ratio of 0.37, so I think it is an active drug. It is an oral agent.
The one thing about the drug that’s very interesting is one of the most common toxicities is ascites. However, when you look at the trial, the placebo arm experienced almost as much ascites as the treatment arm. One question remains, is this molecular change, which is an IDH mutation, potentially resulting in more peritoneal involvement in ascites than other tumor types? We do not know the answer. But the important thing is careful attention to management of ascites in this patient population. The drug is also associated with nausea, vomiting, diarrhea, and loss of taste and appetite. Those are toxicities that as oncologists we are feel more familiar with and more comfortable managing them. However, one cannot argue with the fact that we now have a targeted drug for patients with IDH mutations. Testing is the only way you’re going to find these patients with these molecular alterations.
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.
