Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
JAMA Netw Open. 2023 Jan 3;6(1):e2250030. doi: 10.1001/jamanetworkopen.2022.50030.
Professional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain mutations. Since most studies of first-line targeted therapies have been limited by sample size, there is a need for larger studies using data from routine clinical care.
To identify factors associated with receipt of first-line targeted therapies among patients with metastatic colorectal cancer for whom RAS or BRAF mutation data in the tumor were available and investigate whether targeted therapy is associated with survival.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used deidentified data from an electronic health record-derived database to include patients from 800 sites of patient care across the US who were diagnosed with de novo metastatic colorectal cancer between January 1, 2013, and March 31, 2020 (n = 9134).
Receipt of first-line targeted therapy, categorized as ever having received EGFR inhibitors, VEGF inhibitors, or neither. The secondary outcome was overall survival.
The study population included 9134 patients. The median age at diagnosis was 62 years (IQR, 53-71 years), 5019 (54.9%) were male, and 5692 (62.3%) were White. The median follow-up period was 15 months. Overall, 713 patients (7.8%) received EGFR inhibitors and 5081 patients (55.6%) received VEGF inhibitors as part of their first-line treatment. Among patients with RAS wild-type (RAS-WT) tumors, 625 patients (15.5%) received EGFR inhibitors and 2053 patients (50.9%) received VEGF inhibitors. In patients with RAS mutant (RAS-Mut) tumors, 50 patients (1.1%) received EGFR inhibitors and 2682 patients (59.7%) received VEGF inhibitors; among those with BRAF-mutant (BRAF-Mut) tumors, 38 patients (6.3%) received EGFR inhibitors and 346 patients (57.2%) received VEGF inhibitors. More than one-third of the patients (36.6%) received neither EGFR inhibitors nor VEGF inhibitors. Compared with patients younger than age 40 years, those aged 80 years or older had significantly lower odds to receive targeted therapies (EGFR or VEGF inhibitors in patients with RAS-WT tumors: adjusted odds ratio [aOR], 0.53; 95% CI, 0.36-0.79; and VEGF inhibitors in patients with RAS-Mut tumors: aOR, 0.62; 95% CI, 0.42-0.90). Improved survival was associated with EGFR inhibitor therapy in patients with RAS-WT tumors (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98). Unlike in clinical trials, however, no survival benefit was noted with use of VEGF inhibitors among patients with RAS-WT (aHR, 1.00; 95% CI, 0.91-1.11) or RAS-Mut (aHR, 1.01; 95% CI, 0.93-1.10) tumors.
The findings of this study showed mixed results on survival benefits associated with targeted therapy. In addition, given that some of the results differed from those of randomized clinical trials, this study highlights the importance of using data originating from routine clinical care.
专业学会指南建议根据肿瘤中存在或不存在特定突变，使用针对转移性结直肠癌的靶向治疗，包括表皮生长因子受体（EGFR）抑制剂和血管内皮生长因子（VEGF）抑制剂。由于大多数一线靶向治疗的研究受到样本量的限制，因此需要使用来自常规临床护理的数据进行更大规模的研究。
确定在肿瘤中存在 RAS 或 BRAF 突变数据的转移性结直肠癌患者接受一线靶向治疗的相关因素，并研究靶向治疗是否与生存相关。
设计、设置和参与者：这项队列研究使用来自电子健康记录衍生数据库的匿名数据，纳入了 2013 年 1 月 1 日至 2020 年 3 月 31 日期间在美国 800 个患者护理地点诊断为新发转移性结直肠癌的患者（n=9134）。
接受一线靶向治疗，分为曾接受 EGFR 抑制剂、VEGF 抑制剂或两者均未接受的患者。次要结局是总生存期。
研究人群包括 9134 例患者。诊断时的中位年龄为 62 岁（IQR，53-71 岁），5019 例（54.9%）为男性，5692 例（62.3%）为白人。中位随访期为 15 个月。总体而言，713 例（7.8%）患者接受了 EGFR 抑制剂，5081 例（55.6%）患者接受了 VEGF 抑制剂作为一线治疗的一部分。在 RAS 野生型（RAS-WT）肿瘤患者中，625 例（15.5%）患者接受了 EGFR 抑制剂，2053 例（50.9%）患者接受了 VEGF 抑制剂。在 RAS 突变型（RAS-Mut）肿瘤患者中，50 例（1.1%）患者接受了 EGFR 抑制剂，2682 例（59.7%）患者接受了 VEGF 抑制剂；在 BRAF 突变型（BRAF-Mut）肿瘤患者中，38 例（6.3%）患者接受了 EGFR 抑制剂，346 例（57.2%）患者接受了 VEGF 抑制剂。超过三分之一的患者（36.6%）既未接受 EGFR 抑制剂也未接受 VEGF 抑制剂。与年龄小于 40 岁的患者相比，80 岁或以上的患者接受靶向治疗的可能性显著降低（RAS-WT 肿瘤患者中接受 EGFR 或 VEGF 抑制剂治疗的患者：调整后的优势比[aOR]，0.53；95%CI，0.36-0.79；RAS-Mut 肿瘤患者中接受 VEGF 抑制剂治疗的患者：aOR，0.62；95%CI，0.42-0.90）。在 RAS-WT 肿瘤患者中，与接受 VEGF 抑制剂治疗的患者相比，EGFR 抑制剂治疗与生存改善相关（调整后的危险比[aHR]，0.85；95%CI，0.74-0.98）。然而，与临床试验不同的是，在 RAS-WT（aHR，1.00；95%CI，0.91-1.11）或 RAS-Mut（aHR，1.01；95%CI，0.93-1.10）肿瘤患者中，使用 VEGF 抑制剂并未观察到生存获益。
这项研究的结果显示，靶向治疗与生存获益相关的结果喜忧参半。此外，由于一些结果与随机临床试验的结果不同，因此这项研究强调了使用源自常规临床护理的数据的重要性。
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