帕尼单抗联合最佳支持治疗与单纯最佳支持治疗用于化疗难治性转移性结直肠癌患者的开放标签III期试验。

Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer.

作者信息

Van Cutsem Eric, Peeters Marc, Siena Salvatore, Humblet Yves, Hendlisz Alain, Neyns Bart, Canon Jean-Luc, Van Laethem Jean-Luc, Maurel Joan, Richardson Gary, Wolf Michael, Amado Rafael G

机构信息

Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium.

出版信息

J Clin Oncol. 2007 May 1;25(13):1658-64. doi: 10.1200/JCO.2006.08.1620.

DOI:10.1200/JCO.2006.08.1620

PMID:17470858

Abstract

PURPOSE

Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitumumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy.

PATIENTS AND METHODS

We randomly assigned 463 patients with 1% or more EGFR tumor cell membrane staining, measurable disease, and radiologic documentation of disease progression during or within 6 months of most recent chemotherapy to panitumumab 6 mg/kg every 2 weeks plus BSC (n = 231) or BSC alone (n = 232). Tumor assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed could receive panitumumab in a cross-over study.

RESULTS

Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Median PFS time was 8 weeks (95% CI, 7.9 to 8.4) for panitumumab and 7.3 weeks (95% CI, 7.1 to 7.7) for BSC. Mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC. Objective response rates also favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), which was confounded by similar activity of panitumumab after 76% of BSC patients entered the cross-over study. Panitumumab was well tolerated. Skin toxicities, hypomagnesaemia, and diarrhea were the most common toxicities observed. No patients had grade 3/4 infusion reactions.

CONCLUSION

Panitumumab significantly improved PFS with manageable toxicity in patients with chemorefractory colorectal cancer.

摘要

目的

帕尼单抗是一种完全人源化的单克隆抗体，靶向表皮生长因子受体（EGFR）。我们比较了帕尼单抗联合最佳支持治疗（BSC）与单纯BSC对标准化疗后病情进展的转移性结直肠癌患者的疗效。

患者和方法

我们将463例EGFR肿瘤细胞膜染色率达1%或更高、疾病可测量且在最近一次化疗期间或化疗后6个月内有疾病进展的影像学记录的患者，随机分为两组，一组每2周接受6mg/kg帕尼单抗联合BSC（n = 231），另一组仅接受BSC（n = 232）。由盲法中心评估进行肿瘤评估，从第8周开始直至疾病进展。主要终点是无进展生存期（PFS）。次要终点包括客观缓解率、总生存期（OS）和安全性。病情进展的BSC组患者可在交叉研究中接受帕尼单抗治疗。

结果

帕尼单抗显著延长了PFS（风险比[HR]，0.54；95%置信区间，0.44至0.66，[P <.0001]）。帕尼单抗组的中位PFS时间为8周（95%置信区间，7.9至8.4），BSC组为7.3周（95%置信区间，7.1至7.7）。帕尼单抗组的平均（标准误）PFS时间为13.8（0.8）周，BSC组为8.5（0.5）周。客观缓解率也显示帕尼单抗优于BSC；在至少随访12个月后，帕尼单抗组的缓解率为10%，BSC组为0%（P <.0001）。未观察到OS有差异（HR，1.00；95%置信区间，0.82至1.22），这受到76%的BSC组患者进入交叉研究后帕尼单抗类似活性的影响。帕尼单抗耐受性良好。皮肤毒性、低镁血症和腹泻是观察到的最常见毒性。无患者发生3/4级输注反应。