FDA Approves Bosutinib for Chronic-Phase Chronic Myeloid Leukemia

Chronic myeloid leukemia.

The FDA has granted efficacy-accelerated approval of bosutinib monohydrate (Bosulif®, Pfizer) for patients with newly diagnosed chronic-phase Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML).

“Management of chronic myeloid leukemia has changed significantly since the development of tyrosine kinase inhibitors (TKIs), with greatly improved response rates and lower risk of transformation translating into a relative survival similar to that of the general population,” wrote Jorge E. Cortes, MD, Director of the Georgia Cancer Center at Augusta University, and colleagues, in their 2018 publication of the BFORE trial (NCT02130557), on which the approval was based. “Bosutinib is a second-generation TKI.”

The BFORE trial, a two-arm, open-label, randomized, multicenter phase 3 trial, enrolled 536 patients with Ph–positive or Ph–negative newly diagnosed chronic-phase CML. The patients were randomized into two groups, with 268 patients receiving 400 mg bosutinib once daily and 268 patients receiving 400 mg imatinib once daily. The primary end point was efficacy.

By 60 months, bosutinib improved the cumulative major molecular response rate of BCL-ABL1 equal or less than 0.1% compared with imatinib (73.9% vs 64.6%). Bosutinib also showed a better cumulative molecular response compared with imatinib (58.2 vs 48.1 for BCL-ABL1 equal or less than 0.01%; 47.4 vs 36.6 for BCL-ABL1 equal or less than 0.0032%).

The most common adverse reactions occurring in at least 20% of patients were diarrhea, rash, nausea, abdominal pain, vomiting, fatigue, hepatic dysfunction, respiratory tract infection, pyrexia, and headache. The most common laboratory abnormalities occurring in at least 20 percent of patients were creatinine increase, hemoglobin decrease, lymphocyte count decrease, platelets decrease, absolute neutrophil count decrease, AST increase, glucose increase, phosphorus decrease, urate increase, alkaline phosphatase increase, lipase increase, creatine kinase increase, and amylase increase.

“Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML,” wrote Dr. Cortes and colleagues. “These results suggest that bosutinib can be an important alternative for patients with previously untreated chronic-phase CML.”

The recommended dose of bosutinib for newly diagnosed chronic-phase Ph–positive CML is 400 mg orally, once daily, with food.

For More Information

Brümmendorf TH, Cortes JE, Milojkovic D, et al (2020). Bosutinib (BOS) versus imatinib for newly diagnosed chronic- phase (CP) chronic myeloid leukemia (CML): final 5-year results from the Bfore Trial. Blood (ASH Annual Meeting Abstracts). Abstract 46.

Cortes JE, Gambacorti-Passerini C, Deininger MW, et al (2018). Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol, 36(3):231-237. DOI:10.1200/JCO.2017.74.7162

Clinicaltrials.gov (2021). A multicenter phase 3, open-label study of bosutinib versus imatinib in adult patients with newly diagnosed chronic-phase chronic myelogenous leukemia. NLM identifier: NCT01230557.

Bosulif® (bosutinib) prescribing information (2021). Pfizer Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/203341s020lbl.pdf

Image credit: Paulo Henrique Orlandi Mourao. Licensed under CC BY-SA 3.0

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