Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months. Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n ¼ 79) or 400 mg twice-daily (n ¼ 81), or imatinib 400 mg daily (n ¼ 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P ¼ 0.0044 and P ¼ 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P ¼ 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction. Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289.
Bibliographical noteFunding Information:
S-H. Kim reports receiving speakers bureau honoraria from Dae-Woong Pharmaceutic Company. Y.R. Do reports receiving speakers bureau honoraria and reports receiving commercial research grants from Bristol-Myers Squibb and Novartis. C.W. Choi reports receiving commercial research grants from Il-Yang Pharm. D-Y. Kim reports receiving commercial research grants from Ilyang Co. and Roche. A.H. Reksodiputro reports receiving commercial research grants from Il-Yang Pharm. D-W. Kim reports receiving speakers bureau honoraria from Ilyang Co. and Novartis, is a consultant/advisory board member for Bristol-Myers Squibb, Ilyang Co., Novartis and Pfizer, and reports receiving commercial research grants from Ariad Co., Ilyang Co., Novartis and Pfizer. No potential conflicts of interest were disclosed by the other authors. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): J.-Y. Kwak, S.-H. Kim, S.J. Oh, D.Y. Zang, H. Kim, J.-A. Kim, Y.R. Do, H.J. Kim, J.S. Park, C.W. Choi, W.S. Lee, Y.-C. Mun, J.S. Chung, H.-J. Shin, D.-Y. Kim, J. Park, C.W. Jung, U. Bunworasate, N.S. Comia, S. Jootar, P.B. Caguioa, S.-E. Lee, D.-W. Kim Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): J.-Y. Kwak, D.-Y. Kim, C.W. Jung, S.-E. Lee, D.-W. Kim Writing, review, and/or revision of the manuscript: J.-Y. Kwak, S.-H. Kim, D.Y. Zang, J.-A. Kim, Y.R. Do, C.W. Choi, W.S. Lee, Y.-C. Mun, J.H. Kong, J.S. Chung, D.-Y. Kim, J. Park, C.W. Jung, A.H. Reksodiputro, D.-W. Kim Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S. Jootar, A.H. Reksodiputro, D.-W. Kim Study supervision: A.H. Reksodiputro, D.-W. Kim We thank the patients and investigators for their participation in the trial and the Korea Leukemia Bank for biomaterial banking and analysis (NRF-2013M3A9B8031236). This study was funded by IL-YANG Pharmaceutical Co., Ltd, which also funded medical writing assistance. Professional medical writing and editorial assistance were provided by Lauren Gallagher, PhD, and Emilia Raszkiewicz of StemScientific, an Ashfield company, with funding from IL-YANG Pharmaceutical Co., Ltd. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.