Georgia Cancer Center, Augusta, CA, USA.
Otto-von-Guericke University Medical Center Magdeburg, Magdeburg, Germany.
J Hematol Oncol. 2020 Jul 14;13(1):92. doi: 10.1186/s13045-020-00929-8.
The phase 2 BRIGHT AML 1003 trial evaluated efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized patients to receive glasdegib + LDAC (n = 78) or LDAC alone (n = 38). The rate of complete remission (CR) was 19.2% in the glasdegib + LDAC arm versus 2.6% in the LDAC arm (P = 0.015).
This post hoc analysis determines whether the clinical benefits of glasdegib are restricted to patients who achieve CR, or if they extend to those who do not achieve CR.
In patients who did not achieve CR, the addition of glasdegib to LDAC improved overall survival (OS) versus LDAC alone (hazard ratio = 0.63 [95% confidence interval, 0.41-0.98]; P = 0.0182; median OS, 5.0 vs 4.1 months). Additionally, more patients receiving glasdegib + LDAC achieved durable recovery of absolute neutrophil count (≥ 1000/μl, 45.6% vs 35.5%), hemoglobin (≥ 9 g/dl, 54.4% vs 38.7%), and platelets (≥ 100,000/μl, 29.8% vs 9.7%). Transfusion independence was achieved by 15.0% and 2.9% of patients receiving glasdegib + LDAC and LDAC alone, respectively.
Collectively, these data suggest that there are clinical benefits with glasdegib in the absence of CR.
ClinicalTrials.gov NCT01546038 (March 7, 2012).
BRIGHT AML 1003 期临床试验评估了吉西他滨联合低剂量阿糖胞苷（LDAC）在不适合强化化疗的急性髓系白血病患者中的疗效和安全性。这项多中心、开放性研究将患者随机分为吉西他滨联合 LDAC 组（n = 78）或 LDAC 单药组（n = 38）。吉西他滨联合 LDAC 组的完全缓解率（CR）为 19.2%，而 LDAC 组为 2.6%（P = 0.015）。
本事后分析旨在确定吉西他滨的临床获益是否仅限于达到 CR 的患者，或者是否扩展至未达到 CR 的患者。
在未达到 CR 的患者中，与 LDAC 单药相比，吉西他滨联合 LDAC 可改善总生存期（OS）（风险比= 0.63[95%置信区间，0.41-0.98]；P = 0.0182；中位 OS，5.0 个月 vs 4.1 个月）。此外，更多接受吉西他滨联合 LDAC 治疗的患者实现了绝对中性粒细胞计数（≥ 1000/μl，45.6% vs 35.5%）、血红蛋白（≥ 9 g/dl，54.4% vs 38.7%）和血小板（≥ 100，000/μl，29.8% vs 9.7%）的持久恢复。吉西他滨联合 LDAC 组和 LDAC 单药组分别有 15.0%和 2.9%的患者实现输血独立性。
总体而言，这些数据表明在缺乏 CR 的情况下，吉西他滨具有临床获益。
ClinicalTrials.gov NCT01546038（2012 年 3 月 7 日）。
