Metastatic Cholangiocarcinoma: Phase 2 Infigratinib Study and Personal Experience With Infigratinib


Milind Javle, MD, shares his personal experience and insights on the approval and use of infigratinib, an FGFR2 fusion–targeted therapy, in patients with previously treated advanced cholangiocarcinoma.


Milind Javle, MD: In this pivotal trial of infigratinib, enrolled patients were extensively treated. In fact, only about one-third had received 1 prior line of therapy, and the rest had received 2 or more lines of therapy. This was a heavily pretreated population. They were treated with infigratinib, 125 mg daily on a 3 weeks on, 1 week off schedule. The overall response rate in the trial was 23%. Interestingly, we noted that patients who had received fewer lines of therapy had a better response rate compared with those who had received 2 or more lines of therapy. The progression-free survival in this trial was 7 months, the duration of response was 5 months, and overall survival extended to beyond 12 months; this was a pivotal and positive trial. I’ve just described the results of FOLFOX [folinic acid, fluorouracil, oxaliplatin] standard chemotherapy, which are relatively poor in comparison. Therefore, this drug got an accelerated approval from the FDA. The accelerated approval mechanism is a conditional approval that requires a subsequent phase 3 trial, which is being conducted at this time. This is called the PROOF trial. The patients who have not received any prior chemotherapy, treatment-naïve patients, are treated with infigratinib vs gemcitabine and cisplatin in the first-line setting. We are still waiting on the results of this trial, but it’s very exciting that patients like the one described now have an FDA-approved option for the treatment of cholangiocarcinoma with infigratinib. This is now known as Truseltiq, which was only the second drug to be approved by the FDA for cholangiocarcinoma. It is certainly a historic event for treating this disease.

At our institute, we were one of the leading sites for the CBGJ398X2204 trial that included infigratinib. We have treated several patients with this therapy. Most of these patients have done quite well with progressive disease or partial responses. There are some toxicities that are encountered with this drug, but in general these are manageable. The most common toxicities include hyperphosphatemia, or elevation of levels of phosphate, which must be carefully followed and sometimes treated with dietary restriction of phosphate, and chelating agents. Other toxicities include anorexia, alteration in taste, mucositis. There is a very low incidence of diarrhea, alopecia. The 2 important toxicities to watch out for are ocular. The most common ocular toxicity is dry eyes, however there are serious ocular toxicities, including retinal pigment epithelial detachment and central serous retinopathy. These are again rare and mostly grade 1 or 2, but must be carefully followed and watched for.

Transcript edited for clarity.


Case: A 61-Year-Old Woman with Metastatic Cholangiocarcinoma

May 2019

Initial presentation

  • A 61-year-old woman presents with jaundice and changes in stool and urine color.

Clinical workup

  • Enlarged liver is palpable on physical examination
  • Blood work reveals serum levels of CA 19-9 (1400 U/ml), bilirubin 2 mg/dL, ALT 550 U/L, AST 120U/L
  • Patient undergoes CT imaging and is found to have multiple liver masses, consistent with metastatic disease or intrahepatic cholangiocarcinoma (iCCA)
  • Histopathological examination identifies adenocarcinoma, CK7+, CK20-, HepPAR-, TTF- consistent with cholangiocarcinoma or upper GI Primary
  • Patient is diabetic and somewhat non-compliant with her diabetes medication
  • Her ECOG PS is 1

July 2019


  • Patient is treated with chemotherapy (gemcitabine + cisplatin) for 24 weeks.
  • Patient is monitored for disease progression every 2-3 months by CT imaging.

July 2020

  • Patient does well for 1 year after initiation of treatment but now has elevated CA 19-9 levels.
  • MRI scans show several liver and bone lesions but no signs of brain metastases.
  • Lab results are normal (absolute neutrophil count 4,000/mm3, platelets 150,000/ml, hemoglobin 12.1 g/dL
  • Patient undergoes NGS testing (Foundation Medicine, Inc.) and is found to have FGFR2-BICC1 gene fusion
  • Patient meets eligibility criteria for infigratinib phase 2 study and is enrolled in the trial and being treated with infigratinib
  • Patient does not show any signs of disease progression on MRI scans for six months, suggestive of stable disease and CA19-9 levels stay within normal limits.
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