Data from: Effect of methylcobalamin on capecitabine-induced hand-foot syndrome in patients with HER2-negative early breast cancer: A multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

Our objective was to evaluate whether methylcobalamin could effectively
and safely prevent hand-foot syndrome (HFS) in human epidermal growth
factor receptor 2 (HER2)-negative early breast cancer (EBC) patients
receiving adjuvant capecitabine treatment. We conducted a multicentre,
double-blind, randomised, placebo-controlled, phase 3 trial. The trials
were conducted across seven hospitals in China between January 2022 and
February 2024. Study participants were women aged 18 to 75 years with
pathologically confirmed HER2-negative EBC who were scheduled to receive
adjuvant capecitabine therapy. Eligible patients were randomly assigned in
a 1:1 ratio to receive methylcobalamin at a dose of 0.5mg orally, three
times daily, or a placebo for a maximum of 24 weeks. The primary endpoint
was the incidence of grade ≥2 HFS at any time of the first occurrence
during capecitabine treatment in the intention-to-treat analysis. 234
patients were randomly assigned to receive methylcobalamin (n=117) or
placebo (n=117), who were included in the intention-to-treat analysis and
safety analysis. The grade ≥2 HFS occurred in 17 (14.5%) of 117 patients
with methylcobalamin versus 34 (29.1%) of 117 patients with placebo (risk
difference −14.5%, 95% confidence interval −24.9% to −4.1%; one-side
P=0.003). The rate of HFS-related reduction or discontinuation of
capecitabine was 7.7% (9 of 117) in the methylcobalamin group and 13.7%
(16 of 117) in the placebo group (risk difference −6.0%, 95% confidence
interval −13.9% to 1.9%). Two groups showed similar incidence of any other
adverse events (88 [75.2%] in the methylcobalamin group and 95 [81.2%] in
the placebo group). No methylcobalamin-specific adverse events were
observed. Oral methylcobalamin, compared to placebo, significantly lowered
the severity of HFS by reducing the incidence of grade ≥2 HFS without
unexpected safety concerns in women with HER2-negative EBC receiving
adjuvant capecitabine treatment. The findings support the use of
methylcobalamin to prevent capecitabine-associated severe HFS in this
patient population. Trial is registered with ClinicalTrials.gov as
NCT05165069.

本研究旨在评估甲钴胺（methylcobalamin）能否有效且安全地预防接受辅助卡培他滨治疗的人类表皮生长因子受体2（HER2）阴性早期乳腺癌（EBC）患者发生手足综合征（HFS）。我们开展了一项多中心、双盲、随机、安慰剂对照的Ⅲ期临床试验。该试验于2022年1月至2024年2月期间在中国7家医院开展。研究对象为年龄18至75岁、经病理学确诊为HER2阴性早期乳腺癌且计划接受辅助卡培他滨治疗的女性患者。符合入组标准的患者以1:1的比例随机分配至两组，分别口服甲钴胺0.5mg、每日3次，或安慰剂，最长干预周期为24周。本研究的主要终点为意向治疗分析中，卡培他滨治疗期间任意时间首次发生≥2级手足综合征的发生率。本研究共纳入234例经随机分配的患者，其中甲钴胺组117例、安慰剂组117例，全部纳入意向治疗分析与安全性分析。结果显示，甲钴胺组117例患者中17例（14.5%）发生≥2级手足综合征，安慰剂组117例患者中34例（29.1%）发生该不良反应；风险差为-14.5%，95%置信区间为-24.9%至-4.1%（单侧P=0.003）。卡培他滨相关手足综合征导致的给药减量或停药率，甲钴胺组为7.7%（117例中9例），安慰剂组为13.7%（117例中16例）；风险差为-6.0%，95%置信区间为-13.9%至1.9%。两组其他任意不良事件的发生率相近：甲钴胺组为75.2%（117例中88例），安慰剂组为81.2%（117例中95例），未观察到与甲钴胺特异性相关的不良事件。综上，与安慰剂相比，口服甲钴胺可通过降低≥2级手足综合征的发生率，显著减轻手足综合征的严重程度，且在接受辅助卡培他滨治疗的HER2阴性早期乳腺癌女性患者中未出现未预期的安全性问题。本研究结果支持在该患者群体中使用甲钴胺预防卡培他滨相关的重度手足综合征。本试验已在美国临床试验数据库（ClinicalTrials.gov）注册，编号为NCT05165069。