Mount Vernon Cancer Centre, Northwood, UK.
Comprehensive Clinical Trials Unit at UCL, London, UK.
Gynecol Oncol. 2020 Dec;159(3):692-698. doi: 10.1016/j.ygyno.2020.09.048. Epub 2020 Oct 16.
We investigated the safety and efficacy of a combination of the oral tyrosine kinase inhibitor, nintedanib (BIBF 1120) with oral cyclophosphamide in patients with relapsed ovarian cancer.
Patients with relapsed ovarian, fallopian tube or primary peritoneal cancer received oral cyclophosphamide (100 mg o.d.) and were randomised (1,1) to also have either oral nintedanib or placebo. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), response rate, toxicity, and quality of life.
117 patients were randomised, 3 did not start trial treatment, median age 64 years. Forty-five (39%) had received ≥5 lines chemotherapy. 30% had received prior bevacizumab. The median OS was 6.8 (nintedanib) versus 6.4 (placebo) months (hazard ratio 1.08; 95% confidence interval 0.72-1.62; P = 0.72). The 6-month PFS rate was 29.6% versus 22.8% (P = 0.57). Grade 3/4 adverse events occurred in 64% (nintedanib) versus 54% (placebo) of patients (P = 0.28); the most frequent G3/4 toxicities were lymphopenia (18.6% nintedanib versus 16.4% placebo), diarrhoea (13.6% versus 0%), neutropenia (11.9% versus 0%), fatigue (10.2% versus 9.1%), and vomiting (10.2% versus 7.3%). Patients who had received prior bevacizumab treatment had 52 days less time on treatment (P < 0.01). 26 patients (23%) took oral cyclophosphamide for ≥6 months. There were no differences in quality of life between treatment arms.
This is the largest reported cohort of patients with relapsed ovarian cancer treated with oral cyclophosphamide. Nintedanib did not improve outcomes when added to oral cyclophosphamide. Although not significant, more patients than expected remained on treatment for ≥6 months. This may reflect a higher proportion of patients with more indolent disease or the higher dose of cyclophosphamide used.
Clinicaltrials.govNCT01610869.
我们研究了口服酪氨酸激酶抑制剂尼达尼布（BIBF 1120）联合口服环磷酰胺在复发性卵巢癌患者中的安全性和疗效。
复发性卵巢癌、输卵管癌或原发性腹膜癌患者接受口服环磷酰胺（100mg 每日）治疗，并随机（1：1）接受口服尼达尼布或安慰剂治疗。主要终点为总生存期（OS）。次要终点包括无进展生存期（PFS）、缓解率、毒性和生活质量。
117 例患者被随机分配，3 例未开始试验治疗，中位年龄 64 岁。45 例（39%）接受了≥5 线化疗。30%的患者曾接受贝伐单抗治疗。中位 OS 为 6.8 个月（尼达尼布）与 6.4 个月（安慰剂）（风险比 1.08；95%置信区间 0.72-1.62；P=0.72）。6 个月 PFS 率为 29.6%与 22.8%（P=0.57）。64%（尼达尼布）与 54%（安慰剂）的患者发生 3/4 级不良事件（P=0.28）；最常见的 3/4 级毒性为淋巴细胞减少症（18.6%尼达尼布与 16.4%安慰剂）、腹泻（13.6%与 0%）、中性粒细胞减少症（11.9%与 0%）、疲劳（10.2%与 9.1%）和呕吐（10.2%与 7.3%）。曾接受贝伐单抗治疗的患者治疗时间减少了 52 天（P<0.01）。26 例（23%）患者口服环磷酰胺治疗时间≥6 个月。治疗组之间的生活质量无差异。
这是报告的最大复发性卵巢癌患者接受口服环磷酰胺治疗的队列。尼达尼布联合口服环磷酰胺不能改善结局。虽然无统计学意义，但预期有更多的患者治疗时间≥6 个月。这可能反映了更多的患者疾病进展缓慢或使用了更高剂量的环磷酰胺。
Clinicaltrials.govNCT01610869。
