Background
Phase III RCT enrolling 536 patients with newly diagnosed Ph+ chronic-phase CML, randomized 1:1 to evaluate first-line bosutinib versus imatinib.
Interventions and follow up
Arm A: Bosutinib 400mg daily
Arm B: Imatinib 400mg daily
Primary endpoint: MMR at 12mo
mFollow up: 12mo (primary analysis)
Arm B: Imatinib 400mg daily
Primary endpoint: MMR at 12mo
mFollow up: 12mo (primary analysis)
Results
12-mo MMR: 47.2% vs 36.9%, P=.02
12-mo CCyR: 77.2% vs 66.4%, P<.001
Transformation to AP/BP CML: rare in both arms (4 vs 6 patients)
OS: NR (immature at 12-mo primary analysis)
12-mo CCyR: 77.2% vs 66.4%, P<.001
Transformation to AP/BP CML: rare in both arms (4 vs 6 patients)
OS: NR (immature at 12-mo primary analysis)
Adverse events
Gastrointestinal/hepatic: Grade ≥3 diarrhea 10.8% vs 3.4%; ALT elevation 19.0% vs 1.5%; AST elevation 9.7% vs 1.9%; elevated lipase 13.1% vs 6.0% (arm A vs B)
Discontinuation: Treatment discontinued in 22.0% vs 26.8%, arm A vs B
Discontinuation: Treatment discontinued in 22.0% vs 26.8%, arm A vs B
Conclusions
First-line bosutinib produced higher and deeper molecular and cytogenetic responses at 12 months than imatinib, with a distinct gastrointestinal and hepatic toxicity profile.
Key Limitations
Short 12-mo primary follow-up; surrogate molecular endpoints without mature OS/PFS data; characteristic GI and transaminase toxicity requiring monitoring; no comparison against other second-generation TKIs.
Clinical Context
Supported FDA/EMA approval of bosutinib for newly diagnosed chronic-phase CML. ELN guidelines include bosutinib as a first-line TKI option; its GI/hepatic profile and lack of significant cardiovascular signal inform selection in patients with cardiovascular comorbidity.