Data_Sheet_3_Characteristics and Absolute Survival of Metastatic Colorectal Cancer Patients Treated With Biologics: A Real-World Data Analysis From Three European Countries.docx

Introduction: Biologics were approved for the treatment of advanced colorectal cancer (CRC) based on favorable benefit-risk-assessments from randomized controlled trials (RCTs), but evidence on their use in the real-world setting is scarce. Based on descriptive analyses we therefore aimed to assess characteristics and survival of CRC patients treated with biologics using large healthcare databases from three European countries (Netherlands, Italy, Germany).
Methods: We included CRC patients treated with a biologic in 2010 or 2014 and characterized them regarding age, sex, comorbidities, and absolute survival.
Results: Among 4,758 patients, the mean age ranged from 64.8 to 66.8 years, the majority was male, and comorbidities used as exclusion criteria in RCTs were coded in up to 30% of these patients. The proportion of bevacizumab users decreased between 2010 (72–93%) and 2014 (63–85%). In 2014, the absolute 12-month survival in new users was 64% (95% CI 51–77%), 56% (30–80%), and 61% (58–63%) in the Dutch, Italian, and German database, respectively, varying by age and comorbidity.
Conclusions: Our study suggests that in the real-world setting, CRC patients treated with biologics are older and less selected regarding comorbidities compared to patients in RCTs, potentially explaining the relatively low 12-month survival we found. Treatment decisions in the real-world setting may require careful evaluation given that the risk-benefit ratio may vary depending on age and co-existing conditions.

引言：生物制剂（Biologics）获批用于晚期结直肠癌（colorectal cancer, CRC）的治疗，其依据为随机对照试验（randomized controlled trials, RCTs）所给出的良好获益风险评估结果，但目前关于此类药物在真实世界临床场景中的应用证据仍较为匮乏。为此，本研究依托荷兰、意大利、德国三个欧洲国家的大型医疗数据库，通过描述性分析评估接受生物制剂治疗的结直肠癌患者的临床特征与生存情况。

研究方法：本研究纳入2010年或2014年接受生物制剂治疗的结直肠癌患者，并从年龄、性别、合并症及绝对生存率（absolute survival）方面对其进行特征描述。

研究结果：本研究共纳入4758例患者，其平均年龄介于64.8至66.8岁之间，多数为男性；随机对照试验中作为排除标准的合并症在多达30%的该类患者中被记录。贝伐珠单抗（bevacizumab）使用者的占比从2010年的72%~93%下降至2014年的63%~85%。2014年，荷兰、意大利、德国数据库中新使用者的12个月绝对生存率分别为64%（95%置信区间(confidence interval, CI)：51%~77%）、56%（30%~80%）及61%（58%~63%），且生存率随年龄与合并症情况存在差异。

结论：本研究提示，相较于随机对照试验中的入组患者，真实世界临床场景中接受生物制剂治疗的结直肠癌患者年龄更大，且合并症筛选标准更为宽松，这或可解释本研究中观察到的相对较低的12个月生存率。鉴于风险获益比会随年龄及合并症情况发生变化，真实世界中的治疗决策需进行审慎评估。