Koukakis Reija, Gatta Francesca, Hechmati Guy, Siena Salvatore
Biostatistics, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex, UB8 1DH, UK.
Global Health Economics, Amgen (Europe) GmbH, Zug, Switzerland.
Qual Life Res. 2016 Oct;25(10):2645-2656. doi: 10.1007/s11136-016-1288-4. Epub 2016 Apr 15.
Epidermal growth factor receptor inhibitors such as panitumumab are associated with characteristic skin toxicities. We summarise data from three panitumumab clinical trials to investigate the potential impact of skin toxicity on quality of life (QoL) in patients with metastatic colorectal cancer (mCRC).
The studies were randomised, open-label trials comparing standard treatment (first-line FOLFOX4 [n = 456], second-line FOLFIRI [n = 381], or best supportive care [n = 114]) with or without panitumumab in adults with KRAS/NRAS (RAS) wild-type mCRC. QoL was assessed using the EuroQoL 5-domain health state index (HSI) and overall health rating (OHR) measures. Impact of skin toxicity on changes in QoL scores was estimated using a linear mixed-effects model. Worst skin toxicity was defined in separate models as a subgroup variable or as a measure over time.
Regardless of analysis method, there were no statistically significant differences between the panitumumab and comparator arms in any of the studies in terms of change in HSI or OHR scores. There were no statistically significant differences in QoL outcomes between patients with worst skin toxicity grade <3 and those with grade ≥3. In addition, there were no statistically significant differences between the panitumumab and comparator arms in subgroups of patients with worst skin toxicity of grade <3 and ≥3.
Addition of panitumumab to chemotherapy in RAS wild-type mCRC has no statistically significant negative effect on overall QoL, despite skin toxicity. Skin toxicity of worst grade ≥3 appeared to have similar impact on QoL as skin toxicity of grade <3.
帕尼单抗等表皮生长因子受体抑制剂会引发典型的皮肤毒性。我们汇总了三项帕尼单抗临床试验的数据,以研究皮肤毒性对转移性结直肠癌(mCRC)患者生活质量(QoL)的潜在影响。
这些研究为随机、开放标签试验,比较了标准治疗(一线FOLFOX4[n = 456]、二线FOLFIRI[n = 381]或最佳支持治疗[n = 114])联合或不联合帕尼单抗用于KRAS/NRAS(RAS)野生型mCRC成人患者的疗效。使用欧洲五维健康状态指数(HSI)和总体健康评分(OHR)评估生活质量。使用线性混合效应模型估计皮肤毒性对生活质量评分变化的影响。在不同模型中,将最严重皮肤毒性定义为亚组变量或随时间变化的指标。
无论采用何种分析方法,在任何一项研究中,帕尼单抗组与对照臂在HSI或OHR评分变化方面均无统计学显著差异。最严重皮肤毒性等级<3的患者与等级≥3的患者在生活质量结果方面无统计学显著差异。此外,最严重皮肤毒性等级<3和≥3的患者亚组中,帕尼单抗组与对照臂之间也无统计学显著差异。
在RAS野生型mCRC患者中,化疗联合帕尼单抗尽管会出现皮肤毒性,但对总体生活质量无统计学显著负面影响。最严重等级≥3的皮肤毒性对生活质量的影响似乎与<3级皮肤毒性相似。