College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, Australia.
Target Oncol. 2019 Dec;14(6):743-748. doi: 10.1007/s11523-019-00683-z.
Studies of patients treated with bevacizumab and other vascular epithelial growth factor (VEGF) inhibitors have reported that hypertension adverse events (AEs) are associated with improved overall survival (OS) or progression-free survival (PFS).
Our objective was to evaluate the association between early AEs and survival outcomes for patients treated with ramucirumab, an antibody targeting the VEGF receptor-2 (VEGFR-2), plus FOLFIRI for metastatic colorectal cancer (mCRC).
Data from 529 patients treated with ramucirumab plus FOLFIRI for mCRC in the RAISE clinical trial (NCT01183780) were evaluated to see whether early (first 6 weeks of therapy) AEs predicted subsequent OS and PFS. A Cox proportional hazard approach was used to evaluate associations between early AEs and survival outcomes. A secondary analysis between FOLFIRI and placebo was conducted as a sensitivity analysis.
Of 529 patients treated with ramucirumab plus FOLFIRI, 479 were alive and progression free at 6 weeks after commencing therapy. No significant association was identified between hypertension occurring within the first 42 days of ramucirumab plus FOLFIRI therapy and OS (grade 1-2, hazard ratio [HR] 0.90 [95% confidence interval (CI) 0.66-1.24]; grade 3+, HR 1.02 [95% CI 0.67-1.55]; P = 0.803) or PFS (grade 1-2, HR 0.98 [95% CI 0.74-1.28]; grade 3+, HR 0.93 [95% CI 0.64-1.37]; P = 0.93). However, there was a significant association between diarrhea occurring within the first 42 days of ramucirumab plus FOLFIRI therapy and worse OS (grade 1-2, HR 0.96 [95% CI 0.76-1.20]; grade 3+, HR 2.72 [95% CI 1.67-4.44]; P = 0.001) and PFS (grade 1-2, HR 1.01 [95% CI 0.83-1.23]; grade 3+, HR 2.22 [95% CI 1.43-3.45]; P = 0.005). No other AEs were significantly associated with OS or PFS.
Ramucirumab-induced hypertension was not associated with improved OS and PFS in patients with mCRC treated with ramucirumab and FOLFIRI, but severe diarrhea was associated with poorer OS and PFS.
No. NCT01183780.
接受贝伐珠单抗和其他血管内皮生长因子（VEGF）抑制剂治疗的患者研究报告称，高血压不良事件（AE）与总生存期（OS）或无进展生存期（PFS）的改善相关。
我们的目的是评估雷莫芦单抗（一种针对血管内皮生长因子受体-2（VEGFR-2）的抗体）联合 FOLFIRI 治疗转移性结直肠癌（mCRC）患者的早期 AE 与生存结局之间的关系。
对 RAISE 临床试验（NCT01183780）中 529 例接受雷莫芦单抗联合 FOLFIRI 治疗 mCRC 的患者的数据进行评估，以确定早期（治疗的前 6 周）AE 是否预测随后的 OS 和 PFS。采用 Cox 比例风险方法评估早期 AE 与生存结局之间的关联。进行 FOLFIRI 和安慰剂之间的二次分析作为敏感性分析。
在 529 例接受雷莫芦单抗联合 FOLFIRI 治疗的患者中，有 479 例在开始治疗后 6 周时存活且无进展。雷莫芦单抗联合 FOLFIRI 治疗的前 42 天内发生的高血压与 OS（1-2 级，风险比 [HR]0.90 [95%置信区间 [CI]0.66-1.24]；3+级，HR 1.02 [95%CI 0.67-1.55]；P=0.803）或 PFS（1-2 级，HR 0.98 [95%CI 0.74-1.28]；3+级，HR 0.93 [95%CI 0.64-1.37]；P=0.93）之间无显著关联。然而，雷莫芦单抗联合 FOLFIRI 治疗的前 42 天内发生腹泻与较差的 OS（1-2 级，HR 0.96 [95%CI 0.76-1.20]；3+级，HR 2.72 [95%CI 1.67-4.44]；P=0.001）和 PFS（1-2 级，HR 1.01 [95%CI 0.83-1.23]；3+级，HR 2.22 [95%CI 1.43-3.45]；P=0.005）显著相关。其他 AE 与 OS 或 PFS 无显著相关性。
在接受雷莫芦单抗联合 FOLFIRI 治疗的 mCRC 患者中，雷莫芦单抗引起的高血压与 OS 和 PFS 的改善无关，但严重腹泻与 OS 和 PFS 较差相关。
NCT01183780。
