Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase 3, Randomized, Open-label, Multi-center FESTnd Study
Mené sur 394 patients atteints d’une leucémie myéloïde chronique en phase chronique récemment diagnostiquée, cet essai de phase III compare l’efficacité, du point de vue du taux de réponse moléculaire majeure, et la toxicité du flumatinib et de l’imatinib en traitement de première ligne
Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP). Experimental Design: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n=196) or imatinib 400 mg once daily (n=198). Results: The rate of major molecular response (MMR) at 6 months (primary end point) was significantly higher with flumatinib than with imatinib (33.7% vs 18.3%, P=0.0006), as was the rate of MMR at 12 months (52.6% vs 39.6%, P=0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs 53.3%, P<0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved MR4 at 6, 9 and 12 months (8.7% vs 3.6%, P=0.0358; 16.8% vs 5.1%, P=0.0002; 23.0% vs 11.7%, P=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, faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP.