The first targeted drug of cholangiocarcinoma, peimitinib, has both efficacy and safety -- The final results of FIGHT-202

Cholangiocarcinoma is a kind of refractory and high malignant tumor, with a very high mortality rate. The 5-year survival rate of patients with advanced stage is only 5%. In recent years, with the continuous development of targeted drugs, pemigatinib, as the world's first and only targeted drug approved by the US FDA for the treatment of cholangiocarcinoma, has come out, bringing new hope to patients with cholangiocarcinoma. From September 1 to 4, 2022, at the 16th International Liver Cancer Association Annual Meeting (ILCA 2022) held in Spain, Professor Ghassan Abou Alfa of the Sloan Kettering Cancer Center in memory of the United States orally reported the latest progress in the treatment of locally advanced or metastatic cholangiocarcinoma with pemetinib - the final results of the FIGHT-202 study, which attracted wide attention. At the meeting, we invited Professor Abou Alfa to conduct an exclusive interview on the current treatment strategy of cholangiocarcinoma, the results of the FIGHT-202 study and its clinical significance. Now we have compiled the contents into an article for the readers.

 Interview with Professor Ghassan Abou Alfa of Memorial Sloan Kettering Cancer Center

Please tell us about the incidence and prognosis of cholangiocarcinoma? What is the status of its diagnosis and treatment?At present, what are the main strategies for the treatment of cholangiocarcinoma?

Dr Abou-Alfa: Cholangiocarcinoma is a cancer that affects the bile ducts inside the liver. It can also occur outside the liver. We call it intrahepatic or extrahepatic. If we are to focus on the intrahepatic cholangiocarcinoma, which is the most common form, sadly, the incidence is on the rise for many reasons. Some of them, admittedly, we don’t understand, but most importantly, there is a better understanding of the disease and better diagnosis of the disease. The important thing to recognize is that early disease and complete resection will better ensure a cure for the patient. Sadly for a lot of patients, they either recur or they present with advanced disease and require systemic therapy. Systemic therapy has evolved very rapidly for cholangiocarcinoma and involves several methods including chemotherapy, biologic therapy, as well as immunotherapy.

As we discussed, chemotherapy remains an important base for treatment, with the standard being gemcitabine plus cisplatin therapy based on the ABC-02 study. Adding on to chemotherapy is not yet validated, but nonetheless we are waiting for some important data, such as the SWOG 1815 study of gemcitabine and cisplatin plus nab-paclitaxel. On the other hand though, next generation sequencing is a critical component. If you remember anything from today, be sure to check on next generation sequencing for patients as early as possible, and for many genetic alterations we have therapies available. It is important to identify the right therapy for the patient when needed, such as anti-FGFR2, anti-IDH1 and anti-ERBB2, and so on. The newest approach though is the addition of immunotherapy to chemotherapy. This shook things up and surprised us all. It definitely now poses the question of where to place all these lines of treatment.

 

As we known，based on the fight-202 study, in May 2020, the NCCN guidelines recommended pemigatinib for the treatment of locally advanced or metastatic cholangiocarcinoma patients with FGFR2 fusion or rearrangement. Please introduce the design of the study and previous results？

Dr Abou-Alfa: It was a great honor to lead that important study, FIGHT-202, at the Memorial Sloan Kettering Cancer Center in New York, along with our colleagues from all over the world. This is a study that is very critical. It is a phase II clinical trial looking at pemigatinib for FGFR2 inhibition with FGFR fusion, as well as other alterations for better outcomes related to cholangiocarcinoma. The design of the trial enrolled patients into three arms based on their genetic makeup - either with FGFR2 fusion or other FGFR mutations or no mutations at all. The patients with FGFR2 fusion faired the best. Importantly, collectively there was enough positive data from the phase II trial for it to be conditionally approved and included in the NCCN Guidelines as a second-line therapy for patients with advanced cholangiocarcinoma with FGFR2 fusion or other genetic alterations.

 

 

At ILCA 2022 annual meeting, you will present the final results of fight-202. Could you please introduce the following in detail? What is the clinical significance of this result?

Dr Abou-Alfa: On behalf of my colleagues and co-authors, I am greatly delighted to be here in Madrid for the International Liver Cancer Association Meeting, and we are delighted to present the latest data on the FIGHT-202 study. The good news is, the study remains very positive and is still very promising in supporting the conditions for which it was included in the NCCN Guidelines. The response rates remain robust (close to 28+%) with a duration of response of 9 months or so, and impressively, an overall survival of 17.5 months. There is no doubt that for patients with FGFR2 fusion, in case they need systemic therapy and to be considered for second-line therapy, pemigatinib is a good choice.

 

At present, are there any other latest developments in the new drug research of FGF inhibitors? Do you think FGF inhibitors is expected to enter the first-line treatment of cholangiocarcinoma in the future?

Dr Abou-Alfa: That is a very important question whether anti-FGFR2 therapy is likely to be a first-line treatment. Biologically, it can make sense. However, the advent of durvalumab plus gemcitabine and cisplatin as first-line therapy is a better option right now. Nonetheless, I would say it is a matter of how we should sequence therapy. Do we need the anti-FGFR2 before the checkpoint inhibitors, or vice versa? So far, we are not clear on that. However, interestingly, after we have looked at a lot of data from prospective trials, second-line may be a better position for pemigatinib, at least for now until we know better. So this is something yet to be answered, but of course, at the moment, if a patient is not eligible for durvalumab or cannot access it, the clinical trials, including the one for pemigatinib, indicate its use as second-line therapy is a great choice.