ONCAlert | Upfront Therapy for mRCC

Key Data for the Use of Fedratinib in MF

Targeted Oncology
Published Online:1:00 PM, Tue December 24, 2019

Rami Komrokji, MD: I think this year we are excited that finally we had our second JAK2 inhibitor approved, fedratinib.

Prithviraj Bose, MD: That’s right.

Rami Komrokji, MD: Can you also just briefly summarize the data with fedratinib and your take on it?

Prithviraj Bose, MD: Sure. Fedratinib was initially looked at in a phase III placebo-controlled trial called the JAKARTA trial. This was also in intermediate-2 and high-risk patients, and here the platelet count could be 50 or higher. It’s a little different from the COMFORT trials in that respect. And it beat placebo for both the 35% spleen volume reduction and the 50% TSS [total symptom score] improvement at 24 weeks. It was around 36% versus 0% or 1% for placebo. That was a clearly positive trial. There was another trial, called JAKARTA2, which is important to understand in the current context because we are all using a lot of ruxolitinib frontline. JAKARTA2 was a single-arm trial, actually noncomparative. These were patients who had received prior ruxolitinib for a minimum of 2 weeks, but the median was more like 10 to 11 months.

Fedratinib was employed at the dosage of 400 mg a day in these patients. There were 97 patients, and here in the intention-to-treat population, they found a 31% rate of SVR [spleen volume reduction] and 27% rate of symptom improvement. Very recently, as we said this year, there has been a reanalysis of these data because it was felt that we needed to look more stringently into why these people got off ruxolitinib. That is, did they really fail ruxolitinib? This was presented at ASCO [American Society of Clinical Oncology Annual Meeting] and EHA [European Hematology Association Congress] 2019, and they divided up the patients by a more rigorous definition of relapsed after ruxolitinib, refractory to ruxolitinib, or intolerant of ruxolitinib. Here again they found a 30% rate of spleen volume reduction with fedratinib and a 27% rate of symptom improvement. Granted, this was a slightly smaller subset than all 97. They had 79 in this analysis, but those numbers pretty much held up.

Rami Komrokji, MD: Absolutely. So where do you see the use of fedratinib now? Where would you use fedratinib in your practice today?

Prithviraj Bose, MD: I think it’s a valuable addition to our armamentarium in the RUX [ruxolitinib] failure setting. To me, the benefits of ruxolitinib are so well established that I will continue to use that as my frontline drug of choice. However, if a patient fails, we have some direction as to what is failure. Although nobody has been able to define it very well, it’s perhaps 1 of the most nebulous areas in myelofibrosis. However, with the reanalysis of JAKARTA2, we at least have a framework of what is failure. And yes, I would use it in those patients.

Transcript edited for clarity.

Rami Komrokji, MD: I think this year we are excited that finally we had our second JAK2 inhibitor approved, fedratinib.

Prithviraj Bose, MD: That’s right.

Rami Komrokji, MD: Can you also just briefly summarize the data with fedratinib and your take on it?

Prithviraj Bose, MD: Sure. Fedratinib was initially looked at in a phase III placebo-controlled trial called the JAKARTA trial. This was also in intermediate-2 and high-risk patients, and here the platelet count could be 50 or higher. It’s a little different from the COMFORT trials in that respect. And it beat placebo for both the 35% spleen volume reduction and the 50% TSS [total symptom score] improvement at 24 weeks. It was around 36% versus 0% or 1% for placebo. That was a clearly positive trial. There was another trial, called JAKARTA2, which is important to understand in the current context because we are all using a lot of ruxolitinib frontline. JAKARTA2 was a single-arm trial, actually noncomparative. These were patients who had received prior ruxolitinib for a minimum of 2 weeks, but the median was more like 10 to 11 months.

Fedratinib was employed at the dosage of 400 mg a day in these patients. There were 97 patients, and here in the intention-to-treat population, they found a 31% rate of SVR [spleen volume reduction] and 27% rate of symptom improvement. Very recently, as we said this year, there has been a reanalysis of these data because it was felt that we needed to look more stringently into why these people got off ruxolitinib. That is, did they really fail ruxolitinib? This was presented at ASCO [American Society of Clinical Oncology Annual Meeting] and EHA [European Hematology Association Congress] 2019, and they divided up the patients by a more rigorous definition of relapsed after ruxolitinib, refractory to ruxolitinib, or intolerant of ruxolitinib. Here again they found a 30% rate of spleen volume reduction with fedratinib and a 27% rate of symptom improvement. Granted, this was a slightly smaller subset than all 97. They had 79 in this analysis, but those numbers pretty much held up.

Rami Komrokji, MD: Absolutely. So where do you see the use of fedratinib now? Where would you use fedratinib in your practice today?

Prithviraj Bose, MD: I think it’s a valuable addition to our armamentarium in the RUX [ruxolitinib] failure setting. To me, the benefits of ruxolitinib are so well established that I will continue to use that as my frontline drug of choice. However, if a patient fails, we have some direction as to what is failure. Although nobody has been able to define it very well, it’s perhaps 1 of the most nebulous areas in myelofibrosis. However, with the reanalysis of JAKARTA2, we at least have a framework of what is failure. And yes, I would use it in those patients.

Transcript edited for clarity.
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