medwireNews: Study findings suggest that bosutinib could be considered as an alternative to imatinib for first-line tyrosine kinase inhibitor (TKI) therapy in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP).
The primary endpoint of the BFORE trial – the modified intention to treat rate of major molecular response (MMR, BCR–ABL1 ≤0.1%) at 12 months – was reached by 47.2% of the 246 patients randomly assigned to receive bosutinib 400 mg/day and 36.9% of the 241 patients given imatinib 400 mg/day, giving a significant odds ratio (OR) of 1.55 in favor of the second-generation TKI.
The rate of complete cytogenetic response (CCyR) at 12 months was also significantly higher with bosutinib than imatinib, at 77.2% versus 66.4% (OR=1.74), and this continued at 2 years with an OR of 1.38.
The findings follow those of the BELA trial in a similar patient population, which also showed a higher CCyR rate at 12 months for bosutinib 500 mg/day than imatinib 400 mg/day, although this was not statistically significant, as well as a better 12-month MMR rate and shorter time to response.
Jorge Cortes, from The University of Texas MD Anderson Cancer Center in Houston, USA, reported that the 12-month MMR rate was higher for patients treated with bosutinib than imatinib regardless of whether patients’ Sokal risk scores were high (34 vs 17%), intermediate (45 vs 39%), or low (58 vs 46%).
He noted that the rate of MMR reached a significant difference between the two treatment groups by the 6-month checkpoint, and that by 12 months bosutinib was associated with a significantly higher rate than imatinib for MR4 (BCR–ABL1 ≤0.01%; 20.7 vs 12.0%) and MR4.5 (BCR–ABL1 ≤0.0032%; 8.1 vs 3.3%).
“It’s too early to assess formally event-free survival and overall survival,” Cortes told delegates of the 2017 annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, USA.
But the 12-month cumulative incidence of death, transformation to accelerated or blast phase CML, loss of hematologic or CCyR response was 3.7 % with bosutinib versus 6.4% for imatinib. The Kaplan–Meier estimated rates of overall survival were 99.6% and 97.9%, respectively.
He added that three bosutinib-treated patients and two imatinib-treated patients met accelerated phase criteria within 2 weeks of the study but that all five continued with their assigned TKI therapy and four have subsequently achieved MMR.
“With these results, I believe that bosutinib could become a very welcome new treatment option for frontline therapy of CP CML,” Cortes summarized.
The presenter also highlighted the effort to reduce side effects in the BFORE trial by use of a slightly lower dose of bosutinib than in the BELA trial, which prescribed the 500 mg/day dose approved for CML patients with resistance or intolerance to prior TKI therapy.
The adverse event profile was as expected for both drugs, Cortes said. Bosutinib patients were twice as likely to have any-grade diarrhea (70 vs 34%) as imatinib patients, but most of these events were grade 1–2 and “highly manageable.”
Bosutinib was also associated with a higher rate of liver function enzyme elevation than imatinib (all-grade, 40 vs 14%; grade ≥3, 24 vs 4%), but a lower rate of any-grade musculoskeletal adverse events (30 vs 59%) and periorbital edema (1 vs 14%).
Overall, bosutinib-treated patients required more dose interruptions (56 vs 36%) and reductions (35 vs 17%), with a median dose delay of 23 versus 15 days. Discontinuation for adverse events was reported for 14% and 9% of the bosutinib and imatinib groups, respectively.
“Results suggest lower dose (400 mg) [bosutinib] is associated with better tolerability and improved outcomes,” Cortes concluded.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group