Radotinib may yield similar long-term overall survival and progression-free survival rates compared with those seen with imatinib among patients with chronic myeloid leukemia (CML), according to long-term study results published in the British Journal of Haematology.

Radotinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, was approved as a first-line therapy for CML based on 12-month results of the phase 3 RERISE study (ClinicalTrials.gov Identifier: NCT01511289), which suggested that the drug conferred superior major molecular response (MMR) rates compared with those seen with imatinib. RERISE evaluated both 300 mg and 400 mg radotinib given twice daily, though at the 12-month analysis, the former appeared preferable because of a superior safety profile. In the present paper, researchers published results after follow-up of at least 48 months.

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Of 241 patients randomly assigned in RERISE, 79 received 300 mg radotinib twice daily, 81 received 400 mg radotinib twice daily, and 81 received 400 mg imatinib once daily. In these cohorts, 42, 40, and 36 patients, respectively, completed the full 48-month treatment regimen. Baseline characteristics were balanced between the groups.

After follow-up of at least 48 months, MMR rates were higher in the 300 mg radotinib (85%) and 400 mg radotinib (83%) groups compared with the imatinib group (75%). There were no significant differences in 48-month overall and progression-free survival rates between the 3 groups.

Although the treatment failure rate was higher in the imatinib group (19%) compared with the 300 mg radotinib (6%; P =.0197) and 400 mg radotinib (5%; P =0.0072) groups, treatment was only discontinued in 2 patients because of a lab abnormality and in 4 patients because of an adverse event. Treatment discontinuation due to lab abnormality or adverse event occurred in 10 and 7 patients, respectively, in the 300 mg radotinib group and in 11 and 9 patients, respectively, in the 400 mg radotinib group.

Grade 3 or 4 adverse events that were more common in patients receiving imatinib included neutropenia, which occurred in 26 patients (32%) in the imatinib group compared with 15 patients (19%) in the 300 mg radotinib group and 19 patients (23%) in the 400 mg radotinib group, and hypophosphatemia, which occurred 16 patients (20%) in the imatinib group compared with 7 patients (9%) in the 300 mg radotinib group and 5 patients (6%) in the 400 mg radotinib group.

There were, however, several adverse events that were more common in the radotinib groups: grade 3 to 4 hyperbilirubinemia occurred in 25 patients (32%) in the 300 mg radotinib group, 36 patients (44%) in the 400 mg radotinib group, and no patients in the imatinib group; increased aspartate aminotransferase occurred in 9 patients (11%) in the 300 mg radotinib group, 7 patients (9%) in the 400 mg radotinib group, and 2 patients (2%) in the imatinib group; increased alanine aminotransferase occurred in 22 patients (28%) in the 300 mg radotinib group, 26 patients (32%) in the 400 mg radotinib group, and 1 patient (1%) in the imatinib group; and hyperglycemia occurred in 9 patients (11%) in the 300 mg radotinib group, 12 patients (15%) in the 400 mg radotinib group, and 4 patients (5%) in the imatinib group.

“At a time when costs of [tyrosine kinase inhibitors] used to treat patients with CML are considerable…, radotinib potentially represents an attractive treatment option,” the researchers wrote. 

Reference

1.     Do YR, Kwak JY, Kim JA, et al. Long-term data from a phase 3 study of radotinib versus imatinib in patients with newly diagnosed, chronic myeloid leukaemia in the chronic phase (RERISE) [published online February 3, 2020]. Br J Haematol. doi:10.1111/bjh.16381