Department of Oncology, Duke University, DUMC, Durham, USA.
Medical Oncology Department, Hospital General Vall d'Hebron, Barcelona, Spain.
Ann Oncol. 2017 Sep 1;28(9):2272-2277. doi: 10.1093/annonc/mdx303.
Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population.
LA-EP2006 is a proposed biosimilar that has been developed for pegfilgrastim, a long-acting form of granulocyte colony-stimulating factor for the prevention of neutropenia. The current analysis reports data pooled from two independent, multinational, prospective, randomized, controlled, double-blind phase III studies of similar design comparing the safety and efficacy of reference pegfilgrastim with LA-EP2006 in patients with breast cancer receiving myelotoxic (neo)adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy and requiring granulocyte colony-stimulating factor.
A total of 624 patients were randomized in the PROTECT-1 and PROTECT-2 studies (NCT01735175; NCT01516736) (LA-EP2006: n = 314; reference: n = 310). Baseline characteristics of patients were well balanced across treatment groups. The primary end point, mean duration of severe neutropenia in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05 ± 1.055 days versus 1.01 ± 0.958 days), with a treatment difference of - 0.04 days [95% confidence interval (CI): -0.19 to 0.11] that met the equivalence criteria (the 95% CI were within the defined margin of ±1 day). Secondary end points, such as the nadir of absolute neutrophil count and the incidence of febrile neutropenia, were also similar between LA-EP2006 and reference pegfilgrastim. The safety and tolerability profile of LA-EP2006 was similar to that observed with reference pegfilgrastim, and there were no reports of neutralizing antibodies.
This pooled analysis confirms, as a part of totality of evidence approach, that the proposed biosimilar pegfilgrastim LA-EP2006 has a comparable efficacy and safety profile to reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy.
NCT01735175 and NCT01516736.
在对拟开发的生物类似药进行功能和理化特性表征后，通过在敏感患者人群中证实与参比产品具有相似的安全性和疗效，可进一步确证生物类似药的相似性。
LA-EP2006 是一种已开发的培非格司亭生物类似药，是一种长效粒细胞集落刺激因子，用于预防中性粒细胞减少症。目前的分析报告了两项独立的、多中心、前瞻性、随机、对照、双盲 III 期研究的数据汇总，这些研究的设计相似，比较了乳腺癌患者使用培非格司亭生物类似药 LA-EP2006 与参比培非格司亭在接受需要粒细胞集落刺激因子的骨髓抑制（新）辅助 TAC（多西他赛、多柔比星和环磷酰胺）化疗的患者中的安全性和疗效。
在 PROTECT-1 和 PROTECT-2 研究（NCT01735175；NCT01516736）（LA-EP2006：n=314；参比：n=310）中，共有 624 名患者被随机分组。治疗组之间的患者基线特征均衡。主要终点，即第一个化疗周期中严重中性粒细胞减少的平均持续时间，LA-EP2006 组和参比组相似（1.05±1.055 天与 1.01±0.958 天），治疗差异为-0.04 天[95%置信区间（CI）：-0.19 至 0.11]，符合等效性标准（95%CI 在定义的±1 天界限内）。LA-EP2006 与参比培非格司亭的次要终点，如绝对中性粒细胞计数的最低点和发热性中性粒细胞减少症的发生率也相似。LA-EP2006 的安全性和耐受性特征与参比培非格司亭相似，并且没有中和抗体的报告。
该汇总分析证实，作为总体证据方法的一部分，拟开发的生物类似药培非格司亭 LA-EP2006 在接受 TAC 化疗的乳腺癌患者中具有与参比培非格司亭相当的疗效和安全性。
NCT01735175 和 NCT01516736。
