Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P < .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.

中文翻译：

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博舒替尼与伊马替尼治疗新诊断的慢性粒细胞白血病：随机 BFORE 试验的结果


目的 Bosutinib 是一种有效的 SRC/ABL 双重激酶抑制剂，被批准用于对先前治疗耐药和/或不耐受的费城染色体阳性慢性粒细胞白血病 (CML) 成人患者。我们评估了博舒替尼与伊马替尼一线治疗慢性期 CML 的疗效和安全性。方法 在这项正在进行的跨国 III 期研究中，536 名新诊断的慢性期 CML 患者按照 1:1 的比例随机分配接受 400 mg 博舒替尼每日一次 (n = 268) 或伊马替尼 (n = 268) 治疗。根据方案，对具有典型 (e13a2/e14a2) 转录本的费城染色体阳性患者（博舒替尼，n = 246；伊马替尼，n = 241）评估疗效。费城染色体阴性/BCR-ABL1 阳性状态的患者以及费城染色体状态未知和/或非典型 BCR-ABL1 转录物类型的患者被排除在该人群之外。结果 12 个月（主要终点）时，伯舒替尼的主要分子缓解 (MMR) 率显着高于伊马替尼（分别为 47.2% 和 36.9%；P = .02），完全细胞遗传学缓解 (CCyR) 率也高出 12月（分别为 77.2% 和 66.4%；P = .0075）。博舒替尼的累积发生率较高（MMR：风险比，1.34；P = .0173；CCyR：风险比，1.38；P < .001），且反应时间较早。接受博舒替尼治疗的四名患者（1.6%）和接受伊马替尼治疗的六名患者（2.5%）经历了疾病进展至加速/急变期。在接受治疗的患者中，22.0% 接受博舒替尼的患者和 26.8% 接受伊马替尼的患者停止治疗，最常见的是由于药物相关毒性（分别为 12.7% 和 8.7%）。伯舒替尼组中 3 级以上腹泻（7.8% vs 0.8%）以及 ALT（19.0% vs 1.5%）和 AST（9.7% vs 1.9%）水平升高更为常见。 心脏和血管毒性并不常见。结论 接受博舒替尼治疗的患者的 MMR 和 CCyR 发生率显着高于接受伊马替尼治疗的患者，且获得缓解的速度更快。与已知的安全性一致，博舒替尼更常见胃肠道事件和转氨酶升高。结果表明，博舒替尼可能是慢性期 CML 的有效一线治疗方法。