The investigators examined data obtained from 4,166 tyrosine kinase inhibitor (TKI)-treated patients who were followed for a median of 13 months.

The study demonstrated that bosutinib was associated with a lower risk of serious TEAEs than other TKIs. "Notably, bosutinib had a reduced rate of TEAEs even when administered as a third-line agent and despite the fact that bosutinib-treated patients were older and had more co-morbidities than patients treated with other TKIs," Dr. Goldberg said.

The management of CML has changed dramatically since the introduction of TKIs, with most patients experiencing cytogenetic and molecular remissions, and more than 90% of them achieving long-term survival in the clinical trial setting. The development of second- and third-generation agents has provided hematologists and oncologists with additional salvage treatment options for nonresponding patients and has also given clinicians the ability to match agents with patient characteristics in order to minimize potential toxicity.

Clinical trials may not be representative of real-world settings

However, most information about TKI therapy in CML is derived from large clinical trials that include restrictive entry criteria with rigorous monitoring and treatment algorithms. Thus, the results of clinical trials may not be representative of treatment patterns or outcomes in real-world settings.

In the study reported at the European Hematology Association meeting, about one third of patients were more than 60 years of age, and most had significant pre-existing morbid conditions. Many of these patients would not have been eligible for clinical trials.

The analysis found that imatinib was the most commonly used first-line agent in the community setting, dasatinib and nilotinib were the most commonly used second-line agents, and bosutinib and ponatinib were the most commonly used third-line agents. Also, bosutinib-treated patients were the oldest (with a median age of 56 years) and had the most co-morbid conditions (with a mean Charlson Co-Morbidity Index score of 6.2). Bosutinib-treated patients were more likely to have a history of vascular occlusive conditions, kidney diseases and pleural effusion at baseline.

However, bosutinib-treated patients had the lowest rates of serious TEAEs, except for diarrhea. In particular, serious cardiovascular events were significantly less common in the bosutinib group. For example, only 1% of them developed treatment-emergent congestive heart failure versus 6% of ponatinib patients. Fluid retention occurred in 3% of bosutinib patients compared to 10% of ponatinib, 6% of dasatinib and 5% of nilotinib patients.

"Thus for the patient with a significant cardiac history, bosutinib may be a good therapeutic option," Dr. Goldberg said.

Only 15% of the bosutinib group discontinued treatment because of serious TEAEs versus 19-29% with the other TKIs.

"We were comforted to find that the overall toxicity profiles of TKIs in CML patients in the real-world setting mirror those seen in clinical trials," Dr. Goldberg added.

He emphasized that the findings need to be confirmed in multivariate analyses and larger sample sizes.

Written by Jill Stein