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Abstract：
BACKGROUND: Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer.
METHODS: Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25.
RESULTS: Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks.
CONCLUSIONS: The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.
BACKGROUND: NCT02393755.
METHODS: Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25.
RESULTS: Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks.
CONCLUSIONS: The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.
BACKGROUND: NCT02393755.
摘要：
背景：Nintedanib是一种酪氨酸激酶抑制剂，在贝伐单抗耐药的结直肠癌模型中具有疗效。这项I/II期研究评估了尼达尼布和卡培他滨在难治性转移性结直肠癌中的推荐II期剂量和疗效。
方法：关键合格标准包括难治性转移性结直肠癌和ECOG表现状态为1或更低。主要终点是18周无进展生存期（PFS）。单侧二项式检验（在α=1时）将观察到的18周PFS与.25的历史对照进行了比较。
结果：纳入42例患者，包括39在推荐的II期剂量。推荐的II期剂量确定为每天两次口服尼达尼布200mg和每天两次口服卡培他滨1000mg/m2。对36例患者的疗效进行了评估。18周PFS为42％（15/36例；P=0.0209）。PFS中位数为3.4个月。中位总生存期为8.9mo。16例（44%）患者出现3/4级不良事件，最常见的疲劳(8%)，掌足底红斑感觉障碍（8％），天冬氨酸转氨酶升高（6%），虚弱（6%），肺栓塞（6%），脱水（6%）。在第1周期，第1天和第3周期，第1天的骨桥蛋白水平以及ΔCCL2水平与18周时的疾病控制相关。
结论：尼达尼布和卡培他滨的联合用药耐受性良好。临床疗效似乎优于regorafenib或盐酸替吡草胺单药治疗。有必要对类似组合进行进一步研究。
背景：NCT02393755。
方法：关键合格标准包括难治性转移性结直肠癌和ECOG表现状态为1或更低。主要终点是18周无进展生存期（PFS）。单侧二项式检验（在α=1时）将观察到的18周PFS与.25的历史对照进行了比较。
结果：纳入42例患者，包括39在推荐的II期剂量。推荐的II期剂量确定为每天两次口服尼达尼布200mg和每天两次口服卡培他滨1000mg/m2。对36例患者的疗效进行了评估。18周PFS为42％（15/36例；P=0.0209）。PFS中位数为3.4个月。中位总生存期为8.9mo。16例（44%）患者出现3/4级不良事件，最常见的疲劳(8%)，掌足底红斑感觉障碍（8％），天冬氨酸转氨酶升高（6%），虚弱（6%），肺栓塞（6%），脱水（6%）。在第1周期，第1天和第3周期，第1天的骨桥蛋白水平以及ΔCCL2水平与18周时的疾病控制相关。
结论：尼达尼布和卡培他滨的联合用药耐受性良好。临床疗效似乎优于regorafenib或盐酸替吡草胺单药治疗。有必要对类似组合进行进一步研究。
背景：NCT02393755。
