Flumatinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: A phase III, randomized, open-label, multi-center FESTnd study

Abstract

Purpose: Flumatinib has been shown to be a more potent nhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated he efficacy and safety of flumatinib versus imatinib, for first-line reatment of chronic phase Philadelphia chromosome–positive hronic myeloid leukemia (CML-CP). Patients and Methods: In this study, 394 patients were random-zed 1:1 to flumatinib 600 mg once daily (n ¼ 196) or imatinib 00 mg once daily (n ¼ 198) groups. Results: The rate of major molecular response (MMR) at months (primary endpoint) was significantly higher with flumainib than with imatinib (33.7% vs. 18.3%; P ¼ 0.0006), as was the ate of MMR at 12 months (52.6% vs. 39.6%; P ¼ 0.0102). At months, the rate of early molecular response (EMR) was signifcantly higher in patients receiving flumatinib than in those receivng imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P ¼ 0.0358; 16.8% vs. 5.1%, P ¼ 0.0002; and 23.0% vs. 11.7%, P ¼ 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm. Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644. See related commentary by Muller, € p. 3.