ASPECCT研究中既往贝伐单抗暴露、皮肤毒性和低镁血症的最终结果及转归：帕尼单抗对比西妥昔单抗用于化疗难治性野生型KRAS外显子2转移性结直肠癌的随机3期非劣效性研究
Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer.
作者信息
Price Timothy, Kim Tae Won, Li Jin, Cascinu Stefano, Ruff Paul, Suresh Attili Satya, Thomas Anne, Tjulandin Sergei, Guan Xuesong, Peeters Marc
机构信息
The Queen Elizabeth Hospital and University of Adelaide, Woodville, SA, Australia.
Asan Medical Center, University of Ulsan, Songpa-Gu, Seoul, South Korea.
出版信息
Eur J Cancer. 2016 Nov;68:51-59. doi: 10.1016/j.ejca.2016.08.010. Epub 2016 Oct 5.
PURPOSE
The primary analysis of the ASPECCT study demonstrated that panitumumab was non-inferior to cetuximab for overall survival (OS) in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). Here, we report the final analysis results of ASPECCT.
PATIENTS AND METHODS
Patients with wild-type KRAS exon 2 mCRC who progressed on or were intolerant to irinotecan- or oxaliplatin-based chemotherapy were randomised to receive panitumumab 6 mg/kg once every 2 weeks or cetuximab (400 mg/m) followed by 250 mg/m weekly. The primary end-point was OS assessed for non-inferiority. Patients were followed for survival for 24 months after the last patient was randomised and a final analysis was conducted. No formal hypothesis testing was done. Post hoc analyses of outcomes by prior bevacizumab exposure, worst-grade skin toxicity (0-1 versus 2-4) and worst-grade hypomagnesaemia (0 versus 1-4) were conducted.
RESULTS
Nine hundred ninety-nine patients were randomised and received ≥1 treatment dose (panitumumab, n = 499; cetuximab, n = 500). Median OS was 10.2 months with panitumumab versus 9.9 months with cetuximab (hazard ratio = 0.94; 95% confidence interval = 0.82-1.07). Median progression-free survival was 4.2 months with panitumumab and 4.4 months with cetuximab (hazard ratio = 0.98; 95% confidence interval = 0.87-1.12). Longer OS was observed for patients with increased skin toxicity and with hypomagnesaemia in both arms. Furthermore, OS was longer for patients with prior bevacizumab exposure treated with panitumumab than with cetuximab. The observed safety profiles were consistent with previous studies.
CONCLUSION
Consistent with the primary analysis, the final analysis of ASPECCT showed panitumumab was non-inferior to cetuximab for OS for patients with chemotherapy-refractory, wild-type KRAS exon 2 mCRC.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT01001377.
目的
ASPECCT研究的初步分析表明，在化疗难治性野生型KRAS外显子2转移性结直肠癌（mCRC）患者中，帕尼单抗在总生存期（OS）方面不劣于西妥昔单抗。在此，我们报告ASPECCT的最终分析结果。
患者与方法
对接受基于伊立替康或奥沙利铂的化疗后病情进展或不耐受的野生型KRAS外显子2 mCRC患者，随机分组，分别接受每2周一次的6 mg/kg帕尼单抗或先给予400 mg/m²西妥昔单抗，随后每周给予250 mg/m²西妥昔单抗。主要终点为评估非劣效性的总生存期。在最后一名患者随机分组后对患者进行24个月的生存随访并进行最终分析。未进行正式的假设检验。对既往使用贝伐单抗情况、最严重级别的皮肤毒性（0 - 1级与2 - 4级）和最严重级别的低镁血症（0级与1 - 4级）的结局进行事后分析。
结果
999例患者被随机分组并接受了≥1个治疗剂量（帕尼单抗，n = 499；西妥昔单抗，n = 500）。帕尼单抗组的中位总生存期为10.2个月，西妥昔单抗组为9.9个月（风险比 = 0.94；95%置信区间 = 0.82 - 1.07）。帕尼单抗组的中位无进展生存期为4.2个月，西妥昔单抗组为4.4个月（风险比 = 0.98；95%置信区间 = 0.87 - 1.12）。在两组中，皮肤毒性增加和低镁血症患者的总生存期更长。此外，既往接受过贝伐单抗治疗的患者接受帕尼单抗治疗后的总生存期长于接受西妥昔单抗治疗后的总生存期。观察到的安全性特征与既往研究一致。
结论
与初步分析一致，ASPECCT的最终分析表明，对于化疗难治性野生型KRAS外显子2 mCRC患者，帕尼单抗在总生存期方面不劣于西妥昔单抗。
试验注册
ClinicalTrials.gov，NCT01001377。
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