On the role of bosutinib/bosutinib as a treatment option for TKI-pretreated chronic myelogenous leukemia

Cancer doctors are currently discussing the role of bosutinib as an alternative treatment option for patients with chronic myelogenous leukemia (CML) who have developed resistance or intolerance to prior TKIs, supported by confirmatory data from the Phase 4 BYOND trial (NCT02228382).

The U.S. Food and Drug Administration (FDA) approved bosutinib in 2012 for the treatment of Philadelphia chromosome (Ph)-positive CML patients who are intolerant or have developed resistance to previous treatments. The recommended dose of bosutinib for this indication is 500 mg once daily. While the 500 mg dose was found to be effective in the outpatient setting, it was later optimized to 400 mg for first-line treatment, where it showed superior efficacy to standard of care imatinib.

The single-arm, open-label, non-randomizedBYOND trial further evaluated the drug's efficacy in patients with chronic myelogenous leukemia pretreated with a TKI. Final results from BYOND were published in the journal in September 2024 and showed that bosutinib produced high response rates and a manageable safety profile in TKI-pretreated CML patients. At any time, 81.1% (95% CI, 73.7%-87.2%) of evaluable patients achieved or maintained a complete cytogenic response (CCyR) with bosutinib. Additionally, 71.8% (95% CI, 63.9%-78.9%), 59.7% (95% CI, 51.4%-67.7%), and 48.3% (95% CI, 40.1%-56.6%) of patients achieved or maintained a major molecular response (MMR), MR4, and MR4.5, respectively, at any time on treatment.

For patients who did not achieve CCyR at baseline63.5% (95% CI, 49.0%-76.4%) of patients achieved CCyR with bosutinib at any time during treatment. 59.5% (95% CI, 47.9%-70.4%), 52.7% (95% CI, 43.0%-62.2%), and 42.7% (95% CI, 34.1%-51.7%) of patients with no MMR, MR4, or MR4.5 at baseline achieved MMR at any time during treatment, respectively. Of note, most patients achieved deeper MRs during bosutinib treatment compared with baseline.

Although early use of bosutinib is associated with high diarrhea rates, which may lead to high treatment dropout rates,The BYOND trial shows the drug can be optimized for long-term effectiveness by customizing and escalating doses as needed. The drug's easy-to-administer safety profile further supports its sustained efficacy, reinforcing bosutinib's role as an important TKI for pretreated CML patients.

Overall,The Phase 4 BEYOND trial demonstrated that bosutinib is clinically active, produces sustained responses, and has a manageable safety profile, reinforcing the role of bosutinib as an important TKI for pretreated CML patients.

Reference materials:https://www.onclive.com/view/dr-jabbour-on-the-role-of-bosutinb-as-a-therapeutic-option-for-tki-pretreated-cml