贝伐珠单抗联合一线化疗方案治疗转移性结直肠癌的真实世界疗效。

Effectiveness of Combining Bevacizumab With First-Line Chemotherapy Regimens for Metastatic Colorectal Cancer in Real-World Practice.

机构信息

Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea.

Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

出版信息

Clin Colorectal Cancer. 2021 Jun;20(2):101-112.e6. doi: 10.1016/j.clcc.2020.10.001. Epub 2020 Oct 28.

DOI:10.1016/j.clcc.2020.10.001

PMID:33223477

Abstract

BACKGROUND

Anti-vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting.

PATIENTS AND METHODS

We retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy.

RESULTS

In an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018).

CONCLUSION

The addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions.

摘要

背景

抗血管内皮生长因子（VEGF）药物与细胞毒性化疗药物联合使用时，已显示出对转移性结直肠癌（mCRC）的临床益处。由于随机对照试验有严格的纳入标准，而且参与者通常与实际患者不同，因此我们在此研究了贝伐单抗作为联合治疗mCRC 的一部分在韩国真实实践环境中的疗效。

方法

我们回顾性评估了在一家三级癌症中心接受一线化疗的 3748 例 mCRC 或复发性结直肠癌伴远处转移的初始诊断患者。主要研究终点为总生存期。我们使用 Cox 回归风险模型和倾向评分匹配（PSM）方法进行多变量分析，以调整任何混杂的临床病理因素。对于在接受一线化疗之前未接受转移性病变局部治疗的患者，也进行了亚组分析。

结果

在初步的粗分析中，如果 FOLFOX 或 FOLFIRI 一线治疗方案联合贝伐单抗，患者的生存结局更好（中位总生存期，3.5 年比 2.3 年；风险比 [HR] 0.66；95%置信区间 [CI] 0.59-0.73；P <.001）。然而，使用 PSM 方法的 Cox 回归风险模型调整分析显示，这些组之间的生存差异无统计学意义（3.0 年比 2.6 年；HR 0.92；95%CI 0.79-1.07；P =.2612）。我们对 2814 例未接受切除术且未行转移瘤切除术的不可切除疾病患者进行了进一步的生存分析，这些患者在化疗前接受了转移性射频消融术。Cox 回归和 PSM 分析表明，贝伐单抗组的生存情况更好（HR 0.82；95%CI 0.71-0.94；P =.005；HR 0.84；95%CI 0.71-0.99；P =.018）。