Roxadustat用于接受非髓系恶性肿瘤化疗患者贫血治疗的第2期开放标签研究

Open-label, Phase 2 study of roxadustat for the treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies

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AMERICAN JOURNAL OF HEMATOLOGY

影响因子:9.9

分区:医学1区 Top / 血液学2区

发表日期:2023 May

作者: John Glaspy, Nashat Y Gabrail, Patricia Locantore-Ford, Tyson Lee, Katharina Modelska, Vivek Samal, David H Henry

DOI: 10.1002/ajh.26865

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摘要

贫血是骨髓抑制性化疗的常见副作用；然而，化疗引起的贫血（CIA）的管理方案仍然不理想。我们在此环境下评估了Roxadustat的疗效和安全性。这项第2期开放标签研究包括患有非髓系恶性肿瘤且伴有CIA（血红蛋白[Hb] ≤10 g/dL）、计划接受持续≥8周同步骨髓抑制性化疗的患者。口服Roxadustat治疗时间不超过16周（起始剂量为2.0或2.5 mg/kg，每4周调整一次剂量）。主要疗效终点为基线起算在16周内，未接受红细胞（RBC）输血的最大平均血红蛋白（Hb）变化。患者被分配到2.0 mg/kg（n=31）或2.5 mg/kg（n=61）的Roxadustat起始剂量，89例患者被评估疗效。两组的最大Hb变化（平均值[标准差]）在未接受RBC输血的情况下分别为2.4（1.5）和2.5（1.5） g/dL。Hb升高≥2 g/dL的中位（范围）时间为71（57-92）天。12例患者（14.5%）接受了RBC输血（第5周至治疗结束）。Roxadustat在不同肿瘤类型和化疗方案中均表现出疗效。深静脉血栓（DVT）和肺栓塞（PE）发生率分别为14例（15.2%）和9例（9.8%），其中3例发生了严重不良事件，均被研究者认定与Roxadustat有关（PE：n=2[2.2%]；DVT：n=1[1.1%]）。Roxadustat能够增加CIA患者的血红蛋白，无论肿瘤类型和化疗方案如何。不良事件的特征与晚期恶性肿瘤患者中的观察一致。

Abstract

Anemia is a common side effect of myelosuppressive chemotherapy; however, chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in this setting. This open-label Phase 2 study included patients with non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had planned concurrent myelosuppressive chemotherapy for ≥8 additional weeks. Oral roxadustat was administered for ≤16 weeks (starting dose 2.0 or 2.5 mg/kg, then titrated every 4 weeks). The primary efficacy endpoint was mean maximum change in Hb within 16 weeks of baseline without red blood cell (RBC) transfusion. Patients were assigned to roxadustat 2.0 (n = 31) or 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The mean (standard deviation) maximum Hb change from baseline without RBC transfusion was 2.4 (1.5) and 2.5 (1.5) g/dL in the roxadustat 2.0 and 2.5 mg/kg groups, respectively. Median (range) time to Hb increase of ≥2 g/dL was 71 (57-92) days. Twelve patients (14.5%) had RBC transfusions (Week 5 to the end of treatment). Roxadustat was efficacious regardless of tumor type and chemotherapy regimen. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 14 (15.2%) and nine (9.8%) patients, respectively, and three had serious adverse events attributed to roxadustat in the opinion of the investigators (PE: n = 2 [2.2%]; DVT: n = 1 [1.1%]). Roxadustat increased Hb in patients with CIA regardless of tumor type and chemotherapy regimen. Adverse events were consistent with observations in patients with advanced-stage malignancies.