Case-Based Peer Perspectives: A 61-Year-Old Woman with Metastatic Cholangiocarcinoma - Episode 4
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