West Cancer Center, Germantown, Tennessee, USA.
Spectrum Pharmaceuticals, Inc., Irvine, California, USA.
Oncologist. 2020 Aug;25(8):e1233-e1241. doi: 10.1634/theoncologist.2020-0105. Epub 2020 Jun 16.
Eflapegrastim, a novel, long-acting recombinant human granulocyte-colony stimulating factor (rhG-CSF), consists of a rhG-CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. Preclinical and phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for neutrophil counts for eflapegrastim versus pegfilgrastim. This open-label phase III trial compared the efficacy and safety of eflapegrastim with pegfilgrastim for reducing the risk of chemotherapy-induced neutropenia.
Patients with early-stage breast cancer were randomized 1:1 to fixed-dose eflapegrastim 13.2 mg (3.6 mg G-CSF) or standard pegfilgrastim (6 mg G-CSF) following standard docetaxel plus cyclophosphamide chemotherapy for 4 cycles. The primary objective was to demonstrate the noninferiority of eflapegrastim compared with pegfilgrastim in mean duration of severe neutropenia (DSN; grade 4) in cycle 1.
Eligible patients were randomized 1:1 to study arms (eflapegrastim, n = 196; pegfilgrastim, n = 210). The incidence of cycle 1 severe neutropenia was 16% (n = 31) for eflapegrastim versus 24% (n = 51) for pegfilgrastim, reducing the relative risk by 35% (p = .034). The difference in mean cycle 1 DSN (-0.148 day) met the primary endpoint of noninferiority (p < .0001) and also showed statistical superiority for eflapegrastim (p = .013). Noninferiority was maintained for the duration of treatment (all cycles, p < .0001), and secondary efficacy endpoints and safety results were also comparable for study arms.
These results demonstrate noninferiority and comparable safety for eflapegrastim at a lower G-CSF dose versus pegfilgrastim. The potential for increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study in patients at higher risk for CIN.
Chemotherapy-induced neutropenia (CIN) remains a significant clinical dilemma for oncology patients who are striving to complete their prescribed chemotherapy regimen. In a randomized, phase III trial comparing eflapegrastim to pegfilgrastim in the prevention of CIN, the efficacy of eflapegrastim was noninferior to pegfilgrastim and had comparable safety. Nevertheless, the risk of CIN remains a great concern for patients undergoing chemotherapy, as the condition frequently results in chemotherapy delays, dose reductions, and treatment discontinuations.
依氟鸟苷，一种新型长效重组人粒细胞集落刺激因子（rhG-CSF），由 rhG-CSF 类似物通过短的聚乙二醇接头与人类 IgG4 Fc 片段缀合而成。临床前和 I 期和 II 期药效学和药代动力学数据显示，依氟鸟苷与培非格司亭相比，对中性粒细胞计数的效力更强。这项开放标签的 III 期试验比较了依氟鸟苷与培非格司亭在降低化疗引起的中性粒细胞减少风险方面的疗效和安全性。
早期乳腺癌患者在接受标准多西他赛加环磷酰胺化疗 4 个周期后，按 1:1 随机分为固定剂量依氟鸟苷 13.2mg（3.6mg G-CSF）或标准培非格司亭（6mg G-CSF）。主要目的是证明依氟鸟苷在第 1 周期重度中性粒细胞减少症（DSN；4 级）的平均持续时间方面不劣于培非格司亭。
符合条件的患者按 1:1 随机分为研究组（依氟鸟苷组，n=196；培非格司亭组，n=210）。依氟鸟苷组第 1 周期重度中性粒细胞减少症的发生率为 16%（n=31），培非格司亭组为 24%（n=51），相对风险降低 35%（p=0.034）。第 1 周期 DSN 的平均差异（-0.148 天）符合非劣效性主要终点（p<0.0001），并且依氟鸟苷也显示出统计学上的优越性（p=0.013）。治疗期间（所有周期，p<0.0001）均维持非劣效性，研究组的次要疗效终点和安全性结果也相似。
这些结果表明，依氟鸟苷在降低 G-CSF 剂量时与培非格司亭相比具有非劣效性和相当的安全性。依氟鸟苷的潜在更强效力可能为 CIN 患者提供更好的临床获益，值得在更高风险的 CIN 患者中进行进一步的临床研究。
化疗引起的中性粒细胞减少症（CIN）仍然是癌症患者面临的一个重大临床难题，他们努力完成规定的化疗方案。在一项比较依氟鸟苷与培非格司亭预防 CIN 的随机、III 期试验中，依氟鸟苷的疗效不劣于培非格司亭，且安全性相当。然而，CIN 的风险仍然是接受化疗的患者非常关注的问题，因为这种情况经常导致化疗延迟、剂量减少和治疗中断。
