Bosutinib — Drug Monograph
Brand names: Bosulif
Drug class: Tyrosine Kinase Inhibitor
Mechanism of Action
Dual BCR-ABL and Src kinase inhibitor. Bosutinib binds the ATP-binding pocket of the Bcr-Abl kinase domain, suppressing its constitutive tyrosine kinase activity — the molecular driver of CML pathogenesis. Unlike imatinib (primarily ABL) and dasatinib (ABL + Src), bosutinib potently inhibits Src family kinases (Src, Lyn, Hck), contributing to activity in imatinib-resistant cases where Src-mediated signaling plays a role. Bosutinib is active against most imatinib-resistant BCR-ABL kinase domain mutations but lacks meaningful activity against the T315I gatekeeper mutation. Importantly,…
FDA Indications
- Newly diagnosed chronic phase (CP) CML in adults (FDA approved December 2017 — BFORE trial: MMR at 12 months 47.2% vs 36.9% for imatinib)
- Chronic phase, accelerated phase, or blast phase CML with resistance or intolerance to prior therapy (FDA approved September 2012 — BELA and BSURF trials)
Common Side Effects
- Diarrhea (70–82% — the dominant and most clinically significant side effect)
- Nausea (35–46%)
- Thrombocytopenia (35–42%)
- Elevated ALT/AST (24–31%)
- Anemia
- Neutropenia
- Vomiting (27%)
- Abdominal pain (25%)
- Fatigue (26%)
- Rash (22%)
- Peripheral edema (13%)
Clinical Pearl
Diarrhea is the most frequent reason for dose reduction and discontinuation with bosutinib — proactive management with loperamide, taking the drug with food, and temporary dose interruption substantially improves tolerability. In the ASCEMBL trial (asciminib vs bosutinib 500 mg in 3rd-line CML), asciminib achieved superior MMR at 24 weeks (29.3% vs 13.2%) with a more favorable toxicity profile, establishing asciminib as the preferred third-line option. Bosutinib lacks T315I activity, so…
Related Therapies & Mechanisms
- Afatinib (Gilotrif) — Tyrosine Kinase Inhibitor
- Alectinib (Alecensa) — Tyrosine Kinase Inhibitor
- Alpelisib (Piqray) — Tyrosine Kinase Inhibitor
- Asciminib (Scemblix) — Tyrosine Kinase Inhibitor