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First-Line Fedratinib Improves PFS in Patients With MF
Study findings suggest that fedratinib, an oral JAK2 inhibitor, significantly improves progression-free survival (PFS) versus placebo as a first-line treatment in patients with myelofibrosis (MF). These data were presented at the EHA2021 Virtual Congress.
According to Claire Harrison, MD, FRCP, FRCPath, Guy’s and St Thomas’ Hospital, London, United Kingdom, and co-investigators, fedratinib improves splenomegaly as well as overall symptoms in patients with intermediate- or high-risk MF, whether it's used as an initial treatment or in patients previously treated with ruxolitinib.
In the phase 3, double-blind JAKARTA trial, first-line treatment with fedratinib 400 mg/day considerably improved spleen volume and MF symptoms compared with placebo at 24 weeks. Similarly, in the phase 2, single-arm JAKARTA2 trial, fedratinib 400 mg/day also improved spleen volume and symptom burden from baseline in patients with MF previously treated with ruxolitinib. Both trials enrolled patients with intermediate- or high-risk MF who had platelet counts ≥50 ×109/L, and an ECOG score of ≤2.
Thus, Dr Harrison et al aimed to determine the PFS and overall survival (OS) of fedratinib 400mg/day in patients with MF from both trials. Of note, a clinical hold from November 2013 terminated both trials early and survival follow-up stopped, with ongoing patients censored at the time of the hold. However, patients in both trials could continue to receive fedratinib until disease progression or unacceptable toxicity.
In JAKARTA, 96 patients were randomized to receive first-line fedratinib 400mg/day and 96 received placebo for 6 or more 4-week cycles. At the end of cycle 6, 71 (74%) patients randomized to placebo crossed-over to fedratinib. When the study was terminated, follow-up was halted for 74 (77%) and 65 (68%) of patients in the fedratinib arm and placebo arm, respectively. The median PFS for fedratinib was 23.2 months and placebo was 17.5 months (hazard ratio [HR] 0.42; 95% CI, 0.23-0.76; P=0.004). The 1-year PFS rates were 83% and 67%, respectively. Median OS was not reached in either arm (HR 0.57; P-0.094). The 1-year and 18-month survival rates in the fedratinib arm were 92% and 87%, respectively, and in the placebo arm were 86% and 80%.
In JAKARTA2, 97 patients with MF resistant or intolerant to ruxolitinib received a starting dose of fedratinib 400mg/day. The median PFS was 13.3 months (95% CI, 8.4-17.1) and 1-year PFS was 59%. The median OS was not reached (95% CI, 17.1-NR). The 1-year and 18-month survival rates were 84% and 67%, respectively.
“Separation of PFS/OS curves between fedratinib and placebo in JAKARTA, despite fedratinib treatment in the placebo arm after crossover, suggest patients may derive greater benefit from early fedratinib use,” wrote Dr Harrison et al.
According to the researchers, fedratinib significantly improved PFS when compared to placebo as a first-line treatment for patients with MF.
“For patients in the JAKARTA2 treated with fedratinib after prior ruxolitinib, median PFS, median OS, and 1-year survival rate compare favorably with outcomes after ruxolitinib discontinuation from a recent analysis of similar patients with MF included in large healthcare databases (6 months, 11.1 months and 47%, respectively)," Dr Harrison and colleagues reported.
"These survival outcomes were greatly impacted by the fedratinib clinical hold. The ongoing FREEDOM and FREEDOM2 trials will further assess survival with fedratinib in patients with MF,” they concluded.—Emily Bader
Harrison C, Kiladjian J, Verstovsek S, et al. Overall and progression-free survival in patients treated with fedratinib as first-line myelofibrosis (MF) therapy and after prior ruxolitinib: Results from the JAKARTA and JAKARTA2 trials. Presented at: the EHA2021 Virtual Congress; June 9-17, 2021; virtual. Oral Abstract S203.
