Image by Difu Wu
CML cells
The US Food and Drug Administration (FDA) has expanded the approved indication for bosutinib (BOSULIF®).
The tyrosine kinase inhibitor (TKI) is now approved to treat adults with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).
Bosutinib has accelerated approval for this indication. The approval was based on molecular and cytogenetic response rates.
Continued approval may be contingent upon verification and confirmation of clinical benefit in an ongoing, long-term follow-up trial.
Bosutinib was first approved by the FDA in September 2012. At that time, the TKI was approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
A 400 mg tablet of bosutinib was recently approved by the FDA, adding to the previously approved 100 mg and 500 mg strengths.
The recommended dose of bosutinib for newly diagnosed patients is 400 mg orally once daily with food.
For patients who are resistant or intolerant to prior TKI therapy, the recommended dose is 500 mg orally once daily with food.
BFORE trial
The approval of bosutinib in adults with newly diagnosed, chronic phase, Ph+ CML was based on the phase 3 BFORE trial. Results from the trial were presented at the 2017 ASCO Annual Meeting.
In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.
As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).
The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.
Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.
At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).
One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.
Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).
Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).
Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial.
Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data used to support regulatory filings for marketing authorization for bosutinib as first-line treatment for patients with chronic phase, Ph+ CML.
With this approval, Avillion is eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize bosutinib globally.
