贝伐单抗在转移性结直肠癌中的实际应用-毒性概况,生存结果和肿瘤侧边性的影响

H. Chibani, K. El Bairi, O. Al Jarroudi, S. Afqir
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引用次数: 4

摘要

靶向血管生成在转移性结直肠癌(mCRC)使用贝伐单抗是一个标准的护理。在几项针对转移性结直肠癌患者的随机和对照研究中,在一线输注氟嘧啶化疗中加入这种靶向生物制剂与更高的总生存期(OS)相关。然而,在资源有限的国家获得这种疗法具有挑战性。在摩洛哥,卫生部和Lalla Salma基金会为支持收入有限的癌症患者作出巨大努力后,引进了贝伐单抗用于这一适应症。在本报告中,基于摩洛哥东部的一项回顾性队列研究,报告了贝伐单抗联合化疗治疗mCRC的实际疗效和安全性。材料和方法选取2014年1月1日至2019年12月31日在摩洛哥Oujda Hassan II区域癌症中心接受一线贝伐单抗治疗的98例mCRC患者的医疗记录档案,采用描述性统计、Kaplan-Meier估计和多变量Cox回归模型进行时间-事件研究。结果毒性主要为I-II级蛋白尿(10%)、出血事件(10%)、血栓栓塞事件(9%)、I-III级高血压(3%),以及其他罕见事件,如气孔愈合延迟、疤痕开裂、肠穿孔和心力衰竭恶化。在生存期方面,整个队列的中位OS和无进展生存期分别为22个月和13个月。贝伐单抗治疗后接受转移瘤切除术的患者的中位总生存期为31个月,而不可切除肝转移患者的中位总生存期为14个月。值得注意的是,我们证明肿瘤侧边性是OS的预测因素[危险比(HR) = 2.452;95% CI: 1.434-4.191, p = 0.001]。此外,与接受少于10次治疗(17个月)的患者相比,接受10至20次或超过20次贝伐单抗治疗的患者的中位生存期分别为24和33个月(log rank p < 0.0001)。这些显著改善的结果也在多变量Cox回归中得到证实。调整协变量后发现贝伐单抗使用与OS有高度显著的关联(HR = 0.518, 95% CI: 0.374-0.717;P < 0.0001)。结论目前的研究证实了这种治疗策略在mCRC中的重要地位。等待更多的前瞻性研究来验证这些发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness
Introduction Targeting angiogenesis in metastatic colorectal cancer (mCRC) using bevacizumab is a standard of care. The addition of this targeted biological agent to first-line infusional fluoropyrimidine-based chemotherapy was associated with superior overall survival (OS) in several randomized and controlled studies for CRC patients in the metastatic setting. However, access to this therapy in countries with limited resources is challenging. In Morocco, bevacizumab was introduced for this indication after considerable efforts of the Ministry of Health and Lalla Salma Foundation to support cancer patients with a limited income. In this report, the real-world efficacy and safety of the combination of bevacizumab with chemotherapy in mCRC are reported based on a retrospective cohort in Eastern Morocco. Material and methods The archives of the medical records of 98 mCRC patients treated with first-line bevacizumab at the Hassan II Regional Cancer Center (Oujda, Morocco) were sampled from 1st January 2014 to 31st December 2019 and analyzed using descriptive statistics, Kaplan-Meier estimation, and a multivariable Cox regression model for a time-to-event study. Results The toxicity profile was dominated by grade I–II proteinuria (10%), bleeding events (10%), thromboembolic events (9%), grade I–III hypertension (3%), and other rare events such as delayed healing of the stoma, scar dehiscence, intestinal perforation, and heart failure deterioration. In terms of survival, median OS and progression-free survival in the whole cohort were 22 and 13 months respectively. Patients who benefited from a metastasectomy after bevacizumab treatment had 31 months of median OS as compared to 14 months in the matched cohort with non-resectable liver metastasis. Notably, we demonstrated that tumor sidedness is a predictive factor of OS [hazard ratio (HR) = 2.452; 95% CI: 1.434–4.191, p = 0.001]. Moreover, the median OS for patients who received between 10 and 20 or more than 20 bevacizumab administrations was 24 and 33 months respectively as compared to those who received less than 10 cures (17 months) (log rank p < 0.0001). These markedly improved outcomes were also confirmed in multivariate Cox regression. A highly significant association of bevacizumab use and OS was found after adjusting for covariates (HR = 0.518, 95% CI: 0.374–0.717; p < 0.0001). Conclusions The current study confirmed the important place of this therapeutic strategy in mCRC. Additional studies with prospective enrollment are awaited to validate these findings.
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