First-Line Bosutinib ‘Provides Benefit Over Imatinib’ For Chronic Phase CML

Bosutinib achieved higher rates of major molecular response and complete cytogenetic response than imatinib in patients with previously untreated chronic myeloid leukaemia in the chronic phase

medwireNews: The second-generation tyrosine kinase inhibitor bosutinib may be an effective first-line therapy for patients with chronic myeloid leukaemia in the chronic phase (CP CML), suggest BFORE trial findings.

The primary endpoint of major molecular response (MMR) at 12 months in the intention-to-treat population, defined as a BCR–ABL1 RNA level of 0.1% or below on the International Scale, was achieved by 47.2% of the 246 patients randomly assigned to receive bosutinib 400 mg/day.

This was significantly higher than the 12-month MMR rate of 36.9% for the 241 patients who were given imatinib 400 mg/day, with an odds ratio (OR) of 1.55 after adjusting for Sokal risk score for survival, say Jorge Cortes, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-workers.

For patients with a high Sokal risk score, the 12-month rate of MMR was higher with bosutinib than imatinib (34.0 vs 16.7%), as it also was for those with intermediate (44.9 vs 39.1%) and low (58.1 vs 46.3%) scores, although none of these differences reached statistical significance.

Bosutinib-treated patients also had higher rates of MMR at 3, 6 and 9 months than their imatinib-treated counterparts, “indicating a shorter time to response”, and were less likely to require a dose escalation because of suboptimal response (17.2 vs 27.5%).

The secondary endpoint of a complete cytogenetic response at 12 months was also significantly higher with bosutinib than imatinib, at 77.2% versus 66.4% and an adjusted OR of 1.74, they report in the Journal of Clinical Oncology.

Progression to acute or blast phase during therapy occurred in 1.6% of patients in the bosutinib arm and 2.5% of the imatinib arm.

Treatment was discontinued by 22.0% of the patients given bosutinib and 26.8% of those using imatinib, with drug-related side effects the most common reason cited (12.7 vs 8.7%). Dose interruption or reduction occurred in 56.3% and 35.8%, respectively.

Of note, bosutinib was associated with higher rates of grade 3 or more episodes of severe diarrhoea (7.8 vs 0.8%) and elevated alanine aminotransferase (19.0 vs 1.5%), with comparable rates of cardiac events at any grade (5.2 vs 5.3%) and grade 3 or higher (0.7 vs 0.4%).

“We conclude that bosutinib 400 mg once daily provides benefit over imatinib, with higher rates of cytogenetic and molecular responses, and that these responses occur earlier”, write Jorge Cortes et al.

“Bosutinib is associated with a favorable toxicity profile, with most [adverse events] being low-grade, manageable, and improving over time”, they add.

“These results suggest that bosutinib can be an important alternative for patients with previously untreated CP CML.”


Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: Results from the randomized BFORE  trial. J Clin Oncol; Advance online publication 1 November 2017. DOI: 10.1200/JCO.2017.74.7162

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