One of the more recent TKIs (tyrosine kinase inhibitors) used to treat CML is Bosulif (bosutinib), which has been approved in many countries for people who have resistance or intolerance to another TKI.
The effectiveness of Bosulif was studied in a phase III trial called BELA (for Bosutinib Efficacy and Safety in Newly Diagnosed CML), which compared the drug to Gleevec in just over 500 people (Cortes and colleagues. J Clin Oncol 2012;30:3486-3492). About 70% taking either Bosulif or Gleevec achieved a complete cytogenetic response (CCyR) in the first year of treatment. Where the two medications differed, however, was in the proportion who achieved a major molecular response (MMR; i.e. a 3-log reduction in BCR-ABL transcripts): 41% reached MMR at one year with Bosulif compared to 27% with Gleevec.
The two medications also differed in their side effects. With Bosulif, the more common side effects included diarrhea (70%), vomiting (70%) and fever (19%) (Gambacorti-Passerini and colleagues. Am J Hematol 2014;89:947-953). However, the side effects often associated with Gleevec were less common, such as swelling around the eyes (2% vs. 14% with Gleevec), swelling of the hands or feet (5% vs. 12%), muscle cramps (5% vs. 22%), and bone pain (4% vs. 11%). So the most common problem with Bosulif was diarrhea, but this was generally mild and responded well to antidiarrheal medications.
Updated two-year results from the BELA trial have now been published (Brummendorf and colleagues. Br J Haematol 2015;168:69-81). The overall rate of CCyR at 24 months was almost identical with Bosulif and Gleevec (79% and 80%). But there was still a better chance of reaching MMR with Bosulif compared to Gleevec (59% vs. 49%).
During the first year of treatment, four people (2%) on Bosulif progressed to accelerated-phase or blast-crisis CML, compared to 10 people (4%) on Gleevec. But during the second year of treatment, no one in the Bosulif group progressed (four people did on Gleevec), suggesting that disease control is well maintained with Bosulif.