Sobrero Alberto F, Maurel Joan, Fehrenbacher Louis, Scheithauer Werner, Abubakr Yousif A, Lutz Manfred P, Vega-Villegas M Eugenia, Eng Cathy, Steinhauer Ernst U, Prausova Jana, Lenz Heinz-Josef, Borg Christophe, Middleton Gary, Kröning Hendrik, Luppi Gabriele, Kisker Oliver, Zubel Angela, Langer Christiane, Kopit Justin, Burris Howard A
Department of Medical Oncology, Ospedale San Martino, Genoa, 16132, Italy.
J Clin Oncol. 2008 May 10;26(14):2311-9. doi: 10.1200/JCO.2007.13.1193. Epub 2008 Apr 7.
To determine whether adding cetuximab to irinotecan prolongs survival in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine and oxaliplatin.
This multicenter, open-label, phase III study randomly assigned 1,298 patients with epidermal growth factor receptor-expressing mCRC who had experienced first-line fluoropyrimidine and oxaliplatin treatment failure to cetuximab (400 mg/m(2) day 1 followed by 250 mg/m(2) weekly) plus irinotecan (350 mg/m(2) every 3 weeks) or irinotecan alone. Primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR), and quality of life (QOL).
Median OS was comparable between treatments: 10.7 months (95% CI, 9.6 to 11.3) with cetuximab/irinotecan and 10.0 months (95% CI, 9.1 to 11.3) with irinotecan alone (hazard ratio [HR], 0.975; 95% CI, 0.854 to 1.114; P = .71). This lack of difference may have been due to post-trial therapy: 46.9% of patients assigned to irinotecan eventually received cetuximab (87.2% of those who did, received it with irinotecan). Cetuximab added to irinotecan significantly improved PFS (median, 4.0 v 2.6 months; HR, 0.692; 95% CI, 0.617 to 0.776; P <or= .0001) and RR (16.4% v 4.2%; P < .0001), and resulted in significantly better scores in the QOL analysis of global health status (P = .047). Cetuximab did not exacerbate toxicity, except for acneform rash, diarrhea, hypomagnesemia, and associated electrolyte imbalances. Neutropenia was the most common severe toxicity across treatment arms.
Cetuximab and irinotecan improved PFS and RR, and resulted in better QOL versus irinotecan alone. OS was similar between study groups, possibly influenced by the large number of patients in the irinotecan arm who received cetuximab and irinotecan poststudy.
确定在先前接受氟嘧啶和奥沙利铂治疗的转移性结直肠癌（mCRC）患者中，将西妥昔单抗添加到伊立替康中是否能延长生存期。
这项多中心、开放标签的III期研究将1298例表皮生长因子受体表达阳性且一线氟嘧啶和奥沙利铂治疗失败的mCRC患者随机分为西妥昔单抗（第1天400mg/m²，随后每周250mg/m²）联合伊立替康（每3周350mg/m²）组或单纯伊立替康组。主要终点是总生存期（OS）；次要终点包括无进展生存期（PFS）、缓解率（RR）和生活质量（QOL）。
各治疗组的中位OS相当：西妥昔单抗/伊立替康组为10.7个月（95%CI，9.6至11.3），单纯伊立替康组为10.0个月（95%CI，9.1至11.3）（风险比[HR]，0.975；95%CI，0.854至1.114；P = 0.71）。这种差异不明显可能是由于试验后的治疗：分配至伊立替康组的患者中有46.9%最终接受了西妥昔单抗（接受该治疗的患者中有87.2%是与伊立替康联合使用）。西妥昔单抗联合伊立替康显著改善了PFS（中位值，4.0对2.6个月；HR，0.692；95%CI，0.617至0.776；P≤0.0001）和RR（16.4%对4.2%；P < 0.0001），并在全球健康状况的QOL分析中取得了显著更好的评分（P = 0.047）。除了痤疮样皮疹、腹泻、低镁血症及相关电解质失衡外，西妥昔单抗未加重毒性。中性粒细胞减少是各治疗组中最常见的严重毒性反应。
与单纯伊立替康相比，西妥昔单抗联合伊立替康改善了PFS和RR，并带来了更好的QOL。各研究组的OS相似，可能受到伊立替康组中大量患者在研究后接受西妥昔单抗和伊立替康治疗的影响。
