KEY TAKEAWAYS
- The 2-arm BFORE Phase 3 trial studied the efficacy and safety of bosutinib and compared it to that of imatinib in treating chronic phase (CP) chronic myeloid leukemia (CML).
- The Primary Outcome Measure of the trial was Major Molecular Response at 12 months, with OS and EFS being among the secondary outcome measures.
- A single dose of Bosutinib daily proved clinically significant in treating CP CML.
After 5 years of follow-up, the phase 3 BFORE trial (NCT02130557) evaluated the effectiveness and safety of bosutinib (BOS) vs. imatinib (IMA) in patients with recently diagnosed chronic phase (CP) chronic myeloid leukemia (CML). Participants received either BOS or IMA in a 1:1 randomization (starting dose: 400 mg QD). After five years (240 weeks) of follow-up, outcomes were evaluated using the Charlson Comorbidity Index (CCI) score (mCCI).
Participants were divided into two groups based on their mCCI scores: 2 (BOS, n=73; IMA, n=72; 2 untreated); and >2 (BOS, n=195; IMA, n=196). The median (range) dose intensity was respectively 396.4 (39583) and 367.2 (74573) mg/day with BOS vs. 400.0 (240765) and 400.0 (189754) mg/day with IMA in patients with mCCI 2 and >2. The median therapy duration was 55.1 and 53.4 months with BOS vs. 55.0 and 55.1 months with IMA.
The percentage of patients with mCCI 2 and >2 who experienced an early molecular response (BCR::ABL1 10% at 3 months) with BOS was 79.4% and 83.8% vs. 56.5% and 71.0% with IMA. Both the BOS- (mCCI 2, n=7; mCCI >2, n=7) and IMA (mCCI 2, n=9; mCCI >2, n=5) arms saw 14 deaths during the study period, and the researchers determined that 3 and 4 of those deaths were due to CML, respectively.
Approximately 98.5% of patients in each treatment arm and across CCI categories experienced treatment-emergent adverse events (TEAEs). The most frequent TEAEs with were diarrhea, muscular spasms, thrombocytopenia, anemia, nausea, increased alanine aminotransferase ([ALT]), and fatigue. Grade 3/4 TEAEs were seen in 69.2% and 84.9% of individuals with CCI 2 and >2, respectively, compared to 55.2% and 62.0% with IMA.
In the BFORE study, a sizable percentage of patients across mCCI scores attained molecular responses with BOS or IMA after 5 years of follow-up, with a similar percentage of patients attaining MMR and MR4.5 in both subgroups. Regardless of baseline comorbidities, these findings support the use of 400 mg once daily BOS in patients with recently diagnosed CP CML.
Source: https://ash.confex.com/ash/2022/webprogram/Paper163276.html
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02130557
Brummendorf, T. H., Lipton, J. H., Milojkovic, D., Stenke, L., Leip, E., Purcell, S., Viqueira, A., & Cortes, J. E. (2022, November 4). 1703 Efficacy and Safety of Bosutinib Vs Imatinib By Charlson Comorbidity Index in Newly Diagnosed Patients with Chronic Myeloid Leukemia. Retrieved February 28, 2023, from https://ash.confex.com/ash/2022/webprogram/Paper163276.html
