Supplementary Material for: Effect of an Outreach Programme on Vandetanib Safety in Medullary Thyroid Cancer

Objectives: Effective management of adverse events (AEs) following vandetanib treatment is important to maximize clinical benefits. We examined whether more frequent contact with vandetanib-treated patients reduced AEs of CTCAE grade 2 or higher. Study Design: In this open-label, multicentre, phase III study, patients with locally advanced or metastatic medullary thyroid cancer were randomized to a patient outreach programme (outreach) or a standard AE monitoring schedule (vandetanib control) for 52 weeks. In addition to standard AE monitoring, patients in the outreach arm were contacted every 2 weeks by telephone/during their clinic visit for specific AE questioning related to diarrhoea, nausea, vomiting, fatigue, headache and rash. Patients received vandetanib at 200 or 300 mg/day, depending on the creatinine levels at screening. Results: Altogether, 205 patients were randomized (outreach, n = 103; vandetanib control, n = 102). This study did not meet its primary objective; the mean percentage of time patients experienced at least one AE of grade 2 or higher was higher for the outreach group (51.65%) than for the vandetanib control group (45.19%); the difference was not statistically significant (t statistic: 1.29; 95% CI -3.44 to 16.37%; p = 0.199). The most frequently reported AEs were diarrhoea (56.9% for the outreach group vs. 46.6% for the vandetanib controls), hypertension (36.3 vs. 31.1%), rash (25.5 vs. 24.3%) and nausea (25.5% vs. 18.4%), and the most frequently reported AEs of grade 2 or higher were hypertension (33.3 vs. 23.3%), diarrhoea (26.5 vs. 24.3%) and dermatitis acneiform (11.8 vs. 9.7%). Conclusions: Additional outreach to patients treated with vandetanib had no impact on the rate or severity of AEs compared to the standard AE monitoring schedule. AEs were consistent with the known safety profile of vandetanib.

研究目的：有效管理凡德他尼 (vandetanib) 治疗后的不良事件 (adverse events, AEs)，是最大化临床获益的核心环节。本研究旨在探讨，与接受凡德他尼治疗的患者增加接触频次，是否能够降低符合不良事件通用术语标准 (CTCAE) 2级及以上标准的不良事件发生率。
研究设计：本项开放标签、多中心Ⅲ期临床试验中，将局部晚期或转移性甲状腺髓样癌患者随机分为患者随访干预组（干预组）与标准不良事件监测组（凡德他尼对照组），随访周期为52周。除常规不良事件监测外，干预组患者每2周通过电话或门诊就诊环节，接受针对腹泻、恶心、呕吐、乏力、头痛及皮疹的专项不良事件问询。患者每日口服凡德他尼的剂量为200mg或300mg，具体剂量根据筛查时的肌酐水平确定。
研究结果：共计205例患者完成随机分组（干预组n=103，凡德他尼对照组n=102）。本研究未达到主要研究终点：干预组患者至少发生1次CTCAE 2级及以上不良事件的平均时间占比为51.65%，高于凡德他尼对照组的45.19%，但组间差异无统计学意义（t统计量=1.29；95%置信区间：-3.44%~16.37%；P=0.199）。最常报告的不良事件为腹泻（干预组56.9% vs 对照组46.6%）、高血压（36.3% vs 31.1%）、皮疹（25.5% vs 24.3%）及恶心（25.5% vs 18.4%）；2级及以上不良事件中最常见的为高血压（33.3% vs 23.3%）、腹泻（26.5% vs 24.3%）及痤疮样皮炎（11.8% vs 9.7%）。
研究结论：与标准不良事件监测方案相比，对接受凡德他尼治疗的患者增加随访干预，并未对不良事件的发生率或严重程度产生显著影响。本研究中观察到的不良事件与凡德他尼已知的安全性特征一致。