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

<i>Objectives:</i> 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. <i>Study Design:</i> 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. <i>Results:</i> 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%). <i>Conclusions:</i> 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），对于最大化临床获益至关重要。本研究旨在探讨对接受凡德他尼治疗的患者增加随访频率，是否能够降低CTCAE（Common Terminology Criteria for Adverse Events）2级及以上不良事件的发生率。
<研究设计>：本研究为一项开放标签、多中心III期临床试验，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项目组（随访组）与标准不良事件监测对照组（凡德他尼对照组），干预周期为52周。除标准不良事件监测外，随访组患者每2周通过电话或门诊就诊时，针对腹泻、恶心、呕吐、疲乏、头痛及皮疹开展针对性不良事件问询。患者每日接受凡德他尼200 mg或300 mg给药，剂量根据筛查时的肌酐水平确定。
<研究结果>：共计205例患者被随机分组（随访组n=103，凡德他尼对照组n=102）。本研究未达到预设主要研究终点：随访组患者出现至少1次2级及以上不良事件的平均时间占比（51.65%）高于凡德他尼对照组（45.19%），组间差异无统计学意义（t统计量：1.29；95%置信区间（95% Confidence Interval, 95% CI）：-3.44%~16.37%；P=0.199）。最常报告的不良事件包括腹泻（随访组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%）；而2级及以上最常报告的不良事件为高血压（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，对凡德他尼治疗患者增加随访干预，未对不良事件的发生率或严重程度产生显著影响。本次研究报告的不良事件与凡德他尼已知的安全性特征一致。