Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial.

Abstract

PURPOSE:

Bosutinib is an oral Src/Abl tyrosine kinase inhibitor. The phase III Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia (BELA) trial compared bosutinib with imatinib in newly diagnosed, chronic-phase chronic myeloid leukemia (CML).

PATIENTS AND METHODS:

A total of 502 patients were randomly assigned 1:1 to bosutinib 500 mg per day or imatinib 400 mg per day.

RESULTS:

The complete cytogenetic response (CCyR) rate at 12 months was not different for bosutinib (70%; 95% CI, 64% to 76%) versus imatinib (68%; 95% CI, 62% to 74%; two-sided P = .601); therefore, the study did not achieve its primary end point. The major molecular response (MMR) rate at 12 months was higher with bosutinib (41%; 95% CI, 35% to 47%) compared with imatinib (27%; 95% CI, 22% to 33%; two-sided P < .001). Time to CCyR and MMR was faster with bosutinib compared with imatinib (two-sided P < .001 for both). On-treatment transformation to accelerated/blast phase occurred in four patients (2%) on bosutinib compared with 10 patients (4%) on imatinib. A total of three CML-related deaths occurred on the bosutinib arm compared with eight on the imatinib arm. The safety profiles of bosutinib and imatinib were distinct; GI and liver-related events were more frequent with bosutinib, whereas neutropenia, musculoskeletal disorders, and edema were more frequent with imatinib.

CONCLUSION:

This ongoing trial did not meet its primary end point of CCyR at 12 months, despite the observed higher MMR rate at 12 months, faster times to CCyR and MMR, fewer on-treatment transformations to accelerated/blast phase, and fewer CML-related deaths with bosutinib compared with imatinib. Each drug had a distinct safety profile.

• Authors: Jorge E Cortes, Dong-Wook Kim, Hagop M Kantarjian, Tim H Brümmendorf, Irina Dyagil, Laimonas Griskevicius, Hemant Malhotra, Christine Powell, Karïn Gogat, Athena M Countouriotis, Carlo Gambacorti-Passerini
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 28 Pg. 3486-92 (Oct 01 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22949154 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Aniline Compounds
• Antineoplastic Agents
• Benzamides
• Nitriles
• Piperazines
• Pyrimidines
• Quinolines
• bosutinib
• Imatinib Mesylate
• Protein-Tyrosine Kinases

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aniline Compounds (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Benzamides
• Humans
• Imatinib Mesylate
• Leukemia, Myeloid, Chronic-Phase (drug therapy)
• Male
• Middle Aged
• Nitriles (adverse effects, therapeutic use)
• Piperazines (adverse effects, therapeutic use)
• Protein-Tyrosine Kinases (adverse effects, therapeutic use)
• Pyrimidines (adverse effects, therapeutic use)
• Quinolines (adverse effects, therapeutic use)
• Young Adult