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Bosutinib superior to imatinib in newly diagnosed chronic myeloid leukemia
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Patients with chronic myeloid leukemia treated with bosutinib had better major molecular response and complete cytogenic response rates compared with those who received imatinib, study data showed.
Patients treated with bosutinib also achieved responses sooner.
“In a phase 1/[phase] 2 study, significant clinical activity was reported with bosutinib [among] patients with CML resistant and/or intolerant to prior tyrosine kinase inhibitors and [among] patients with advanced disease,” Jorge E. Cortes, MD, deputy chair and professor of medicine in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “This led to a randomized trial of bosutinib vs. imatinib as initial therapy for patients with Philadelphia chromosome-positive chronic- phase CML. Despite an improvement in major molecular response rate at 12 months, shorter time to response and a lower rate of transformation to accelerated phase or blast phase with bosutinib, the study’s primary objective (superior rate of complete cytogenic response at 12 months) was not met.”
With the previous study in mind, Cortes and colleagues performed a multinational randomized phase 3 study of 536 patients with previously untreated CML. The researchers randomly assigned patients to receive 400 mg of either bosutinib (n = 268) or imatinib (n = 241) once daily. The study excluded patients with Philadelphia chromosome-negative BCR-ABL1-positive and unknown Philadelphia chromosome status, as well as those with atypical BCR-ABL1 transcript type.
Patients in the bosutinib group had significantly higher major molecular response rates at 12 months compared with those assigned imatinib (47.2% vs. 36.9%; P = .02), as well as a higher complete cytogenic response rate (77.2% vs. 66.4%; P = .0075).
Those assigned to bosutinib also had a favorable cumulative incidence (major molecular response, HR = 1.34; P = .0173; complete cytogenic response, HR = 1.38; P < .001) and had earlier response times.
In the bosutinib group, four patients (1.6%) experienced disease progression to either the accelerated or blast phase, compared with six patients (2.5%) in the imatinib group.
More than one-fifth (22%) of patients assigned to bosutinib and more than one-fourth (26.8%) of patients assigned to imatinib discontinued their treatment, most commonly because of drug-related toxicity (12.7% for bosutinib and 8.7% for imatinib).
Patients assigned to bosutinib had grade 3 or higher diarrhea more frequently (7.8% vs. 0.8%), as well as increased alanine transaminase (19% vs. 1.5%) and aspartate transaminase (9.7% vs. 1.9%) levels.
“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,” Cortes and colleagues wrote. “Bosutinib is associated with a favorable toxicity profile, with most adverse events being low-grade, manageable and improving over time. These results suggest that bosutinib can be an important alternative for patients with previously untreated chronic phase CML.” – by Andy Polhamus
Disclosures: Cortes reports consulting or advisory roles with Amphivena Therapeutics, ARIAD Pharmaceuticals, Astellas Pharma, BioLineRx, Bio-Path Holdings, Bristol-Myers Squibb, Daiichi Sankyo, Novartis and Pfizer; and research funding to his institution from Ambit Biosciences, ARIAD Pharmaceuticals, Arog Phermaceuticals, Astellas Pharma, Bristol-Meyers Squibb, Celator Pharmaceuticals, Celgene, ImmunoGen, Incyte, Novartis, Pfizer and Teva. Please see the full study for a list of all other authors’ relevant financial disclosures.
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