Abstract 1684
Background
The international, phase 3 BELA trial (NCT00574873) evaluated first-line bosutinib vs imatinib in Philadelphia chromosome–positive patients (pts) with chronic phase chronic myeloid leukemia.
Methods
Pts were randomized to receive bosutinib 500 mg once daily (QD) or imatinib 400 mg QD; the primary endpoint was complete cytogenetic response (CCyR) rate at 12 mo. We compared efficacy and safety of bosutinib and imatinib in Indian and non-Indian pts after 48 mo of follow-up. Efficacy was assessed in the intent-to-treat population; safety was assessed in all pts who received ≥1 dose of study drug.
Results
In all, 54 Indian pts (median age 34.5 y; 61% male) and 448 non-Indian pts (median age 48.5 y; 56% male) were randomized to receive bosutinib (n = 25 and n = 225 [2 untreated], respectively) or imatinib (n = 29 and n = 223 [1 untreated]). At 12 mo, major molecular response (MMR) and CCyR rates, respectively, for bosutinib vs imatinib were 44% vs 24% and 72% vs 86% in Indian pts, and 37% vs 26% and 70% vs 66% in non-Indian pts (Table). After 48 mo of follow-up, cumulative MMR and CCyR rates, respectively, for bosutinib vs imatinib were 64% vs 69% and 84% vs 97% in Indian pts, and 68% vs 67% and 78% vs 79% in non-Indian pts. The most frequently reported treatment-emergent adverse events (TEAEs; any grade) with bosutinib were diarrhea (44%) and thrombocytopenia (36%) in Indian pts, and diarrhea (73%) and nausea (39%) in non-Indian pts. 8 pts in the entire study were lost to follow-up while on-treatment; 7 (6 bosutinib; 1 imatinib) were from Indian sites.Table: 1033P
| Indian pts | Non-Indian pts | |||
|---|---|---|---|---|
| Bosutinib n = 25 | Imatinib n = 29 | Bosutinib n = 225 | Imatinib n = 223 | |
| Sokal Risk Group, n (%) | ||||
| Low | 11 (44) | 13 (45) | 77 (34) | 76 (34) |
| Medium | 11 (44) | 13 (45) | 106 (47) | 105 (47) |
| High | 3 (12) | 3 (10) | 42 (19) | 42 (19) |
| Cumulative response, any time on–treatment, % (95% CI) | ||||
| MMR | 64 (45–83) | 69 (52–86) | 68 (61–74) | 67 (61–73) |
| CCyR | 84 (70–98) | 97 (90–100) | 78 (73–84) | 79 (74–84) |
| Response at 12 mo, % (95% CI) | ||||
| MMR | 44 (25–64) | 24 (9–40) | 37 (31–44) | 26 (20–31) |
| CCyR | 72 (54–90) | 86 (74–99) | 70 (64–76) | 66 (60–72) |
| Probability of retaining response at 48 mo (95% CI)* | ||||
| MMR | 80 (49–93) | 100 (100–100) | 93 (86–96) | 98 (93–99) |
| CCyR | 89 (62–97) | 78 (58–90) | 93 (88–96) | 91 (85–95) |
| Transformation to AP/BP CML, n (%) | 1 (4) | 2 (7) | 4 (2) | 10 (5) |
| Overall survival | ||||
| Deaths, n (%) | 1 (4) | 1 (3) | 14 (6) | 14 (6) |
| At 48 mo (95% CI)* | 96 (72–99) | 96 (77–100) | 95 (91–97) | 94 (89–96) |
Kaplan-Meier estimate
AP=accelerated phase; BP=blast phase; CCyR=complete cytogenetic response; CI=confidence interval; CML=chronic myeloid leukemia; MMR=major molecular response
Conclusions
Response rates for bosutinib were comparable between Indian and non-Indian pts. MMR rates were higher for bosutinib vs imatinib at 12 mo, but not 48 mo, in Indian pts; comparison of bosutinib vs imatinib was limited by the small number of Indian pts. TEAEs were consistent with the known bosutinib safety profile, although Indian pts had a lower rate of diarrhea than non-Indian pts.
Clinical trial identification
NCT00574873.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Editorial Acknowledgement
Medical writing support was provided by Emily Balevich, PhD, of Engage Scientific Solutions, and funded by Pfizer.
Disclosure
E. Leip, R.J. Crescenzo: Employment and stock ownership: Pfizer. C. Gambacorti-Passerini: Consultancy: BMS, Pfizer; Honoraria and research funding: Pfizer. J.E. Cortes: Consultancy: Ariad, BMS, ImmunoGen, Novartis, Pfizer; Research funding: Ariad, BMS, ImmunoGen, Novartis, Pfizer, Sun Pharma, Teva. All other authors have declared no conflicts of interest.
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