Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia.

No widely available therapies are approved for CIT.

目前没有广泛可用的治疗CIT的批准疗法。

Methods

We conducted a phase 3, international, double-blind, randomized, placebo-controlledtrial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers.

我们进行了一项3期、国际性、双盲、随机、安慰剂对照试验，涉及持续性 CIT（血小板计数≤85×10^9/L，在试验第1天）的患者，这些患者正在接受基于奥沙利铂的多药细胞毒性化疗治疗胃肠道癌症。

Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles.

患者以2:1的比例随机分配接受romiplostim或安慰剂治疗，为期三个化疗周期。

The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles.

主要终点是第二和第三化疗周期中，CIT诱导的化疗剂量（减少、延迟、遗漏或中断）无变化。

Results

Of the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease.

在随机化的165名患者中（109名在romiplostim组，56名在安慰剂组），75%患有结直肠癌，13%患有胃食管癌，12%患有胰腺癌；romiplostim组中有72%的患者和安慰剂组中有61%的患者处于IV期。

The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval[CI], 4.44 to 23.72; P<0.001) and a risk ratio of 2.77 (95% CI, 1.78 to 4.30; P<0.001).

使用罗米普利司特的患者中，没有因CIT诱导而对化疗剂量进行修改的比例为84%（109名患者中的92名），而使用安慰剂的患者中这一比例为36%（56名患者中的20名），相应的比值比为10.16（95%置信区间[CI]，4.44至23.72；P<0.001），风险比为2.77（95% CI，1.78至4.30；P<0.001）。

Adverse events of grade 3 or higher occurred in 37% of the patients who received romiplostim and in 22% of those who received placebo, which primarily reflected chemotherapy effects.

接受罗米普利司特治疗的患者中，有37%发生了3级或更高级别的不良事件，而在接受安慰剂治疗的患者中这一比例为22%，这主要反映了化疗的效果。

Adverse events that were considered by the investigator to be related to romiplostim or placebo occurred in 12% of patients who received romiplostim and in 7% who received placebo, with the most frequent being nausea (2% in each group) and headache (2% in the romiplostim group); none were serious or led to death or discontinuation of romiplostim, placebo, or chemotherapy.

研究者认为与罗米司亭或安慰剂相关的不良事件发生在12%接受罗米司亭治疗的患者和7%接受安慰剂治疗的患者中，最常见的不良事件是恶心（两组均为2%）和头痛（罗米司亭组为2%）；这些不良事件均不严重，没有导致死亡或导致罗米司亭、安慰剂或化疗的中断。

Thromboembolic events occurred in 2% of patients who received romiplostim and in no patients who received placebo.

接受罗米司亭治疗的患者中有2%发生了血栓栓塞事件，而接受安慰剂治疗的患者中没有发生此类事件。

Conclusions

In this phase 3, placebo-controlledtrial, romiplostim was efficacious in treating CIT.

在这项3期、安慰剂对照试验中，罗米普利司他治疗慢性免疫性血小板减少症是有效的。

(Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.).

(该研究由安进公司和生物医学高级研究与开发管理局资助；RECITE临床试验注册号，NCT03362177。)