Phase III clinical trial (RERISE study) results of efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia

• Main Authors: Jae Yong Kwak, Sung Hyun Kim, Suk Joong Oh, Dae Young Zang, Hawk Kim, Jeong A. Kim, Young Rok Do, Hyeoung Joon Kim, Joon Seong Park, Chul Won Choi, Won Sik Lee, Yeung Chul Mun, Jee Hyun Kong, Joo Seop Chung, Ho Jin Shin, Dae Young Kim, Jinny Park, Chul Won Jung, Udomsak Bunworasate, Narcisa Sonia Comia, Saengsuree Jootar, Arry Harryanto Reksodiputro, Priscilla B. Caguioa, Sung Eun Lee, Dong Wook Kim
• Other Authors: Chonbuk National University, School of Medicine
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/41700
• Institution: Mahidol University

©2017 AACR. 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.