Radotinib was associated with significantly higher complete cytogenetic responses and major molecular responses than imatinib was at a minimum 12 months of follow-up in a randomized, open-label, phase III clinical trialof patients with newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP).
Radotinib, an investigational BCR-ABL1 tyrosine kinase inhibitor developed by IL-YANG Pharmaceuticals, is approved in Korea for the treatment of CML-CP in patients who have failed prior TKIs.
Dr. Jae-Yong Kwak of Chonbuk National University Medical School and Hospital, Jeonju, South Korea, and his colleagues randomized 241 patients to either radotinib 300 mg twice daily (n = 79), radotinib 400 mg twice daily (n = 81), or imatinib 400 mg once daily (n = 81). All three study groups were balanced in regard to baseline age, gender, race, and Sokal risk score.
At a minimum follow-up of 12 months, the proportions of patients receiving a study drug were 86% (69/79) in the radotinib 300 mg twice-daily group, 72% (58/81) in the radotinib 400 mg twice-daily group, and 82% (66/81) in the imatinib 400 mg once-daily group.
The rates of major molecular response at 12 months were significantly higher in patients receiving radotinib 300 mg b.i.d. (52%, P = .0044) and radotinib 400 mg b.i.d. (46%, P = .0342), compared with imatinib (30%), Dr. Kwak reported at the annual meeting of the American Society of Hematology in Orlando.
Among responders, the median times to major molecular response were shorter on radotinib 300 mg b.i.d. (5.7 months) and radotinib 400 mg b.i.d. (5.6 months) than on imatinib (8.2 months). The MR4.5 rates by 12 months were also higher for both radotinib 300 mg b.i.d. (15%) and 400 mg b.i.d. (14%), compared with imatinib (9%). The complete cytogenetic response rates by 12 months were 91% for radotinib 300 mg b.i.d. (P = .0120), compared with imatinib (77%). None of the patients in the study had progressed to accelerated phase or blast crisis at 12 months.
Drug discontinuation due to adverse events (AEs) or laboratory abnormalities occurred in 9% of patients on radotinib 300 mg b.i.d., 20% on radotinib 400 mg b.i.d., and 6% on imatinib.
The major side effects included grade 3/4 thrombocytopenia in 16% of patients receiving radotinib 300 mg b.i.d., 14% on radotinib 400 mg b.i.d., and 20% receiving imatinib. Grade 3/4 neutropenia occurred in 19%, 24%, and 30% for radotinib 300 mg b.i.d., 400 mg b.i.d., and imatinib, respectively.
Overall, grade 3/4 nonlaboratory AEs were uncommon in all groups. The most common nonlaboratory AEs in the radotinib groups were skin rash (about 33% in both), nausea/vomiting (about 23% in both), headache (19% and 31%), and pruritus (19% and 30%). In the imatinib group, the most common adverse events were edema (35%), myalgia (28%), nausea/vomiting (27%), and skin rash (22%).
Dr. Kwak had no relevant disclosures. Some of his colleagues received research funding from IL-YANG Pharmaceutical Co. and Alexion Pharmaceuticals.
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