Pinter Tamás, Klippel Zandra, Cesas Alvydas, Croitoru Adina, Decaestecker Jochen, Gibbs Peter, Hotko Yevhen, Jassem Jacek, Kurteva Galina, Novotny Jan, O'Reilly Seamus, Salek Tomas, Reiner Maureen, Morrow Phuong Khanh, Choi Mi Rim, Whittaker Sadie, Blanke Charles
Department of Oncoradiology, Petz Aladár Teaching Hospital, Györ, Hungary.
Clinical Development, Amgen Inc, Thousand Oaks, CA.
Clin Colorectal Cancer. 2017 Jun;16(2):103-114.e3. doi: 10.1016/j.clcc.2016.08.008. Epub 2016 Sep 7.
Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]).
Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period.
A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300).
Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.
聚乙二醇化重组人粒细胞刺激因子（培非格司亭）在接受化疗加贝伐单抗的结直肠癌（CRC）患者中降低发热性中性粒细胞减少症（FN）风险的作用，此前尚未在前瞻性研究中进行评估。本III期双盲试验评估了培非格司亭与安慰剂相比，在接受贝伐单抗联合一线化疗（FOLFOX[亚叶酸钙、5-氟尿嘧啶、奥沙利铂]或FOLFIRI[亚叶酸钙、5-氟尿嘧啶、伊立替康]）的晚期CRC患者中降低3/4级FN发生率的疗效。
年龄≥18岁的局部晚期或转移性CRC患者，每14天在接受化疗加贝伐单抗后约24小时，按1:1随机分为安慰剂组或6mg培非格司亭组。研究治疗期包括4个周期，但患者可继续治疗≤60个月。主要终点是前4个周期中3/4级FN的发生率。次要终点包括客观缓解率（ORR）、总生存期和无进展生存期，在长期随访期结束时进行分析。
2009年11月至2012年1月，共有845例患者被随机分组（422例接受培非格司亭，423例接受安慰剂）。培非格司亭显著降低了前4个治疗周期中3/4级FN的发生率（培非格司亭组为2.4%；95%置信区间[CI]，1.1%-4.3%；安慰剂组为5.7%；95%CI，3.7%-8.3%；优势比[OR]，0.41；P = 0.014）。两组在ORR（OR，1.15；P = 0.330）、总生存期（风险比，0.94；P = 0.440）和无进展生存期（风险比，0.93；P = 0.300）方面未观察到显著差异。
培非格司亭降低了接受化疗和贝伐单抗的晚期CRC患者的FN发生率。培非格司亭的给药耐受性良好，且对该患者群体的肿瘤反应或生存期无负面影响。
