Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): prespecified interim analysis of a randomized, phase III clinical trial.

patients_and_methods

This multicenter, randomized, double-blind, phase III trial was conducted at 51 hospital sites in China.

这项多中心、随机、双盲、III期试验在中国的51个医院站点进行。

Patients with HER2-positive gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma whose previous therapy containing trastuzumab had failed were randomized (1 : 1) to receive anbenitamab 30 mg/kg or placebo every 3 weeks, in combination with chemotherapy (paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1 of a 21-day cycle, or irinotecan 125 mg/m2 on day 1 and 8 of a 21-day cycle), stratified by combined chemotherapy [taxane (paclitaxel or docetaxel) or irinotecan], HER2 expression [immunohistochemistry (IHC) 3+ or IHC 2+/FISH+], and previous lines of therapy (1 or ≥2).

HER2阳性胃癌或胃食管交界处腺癌患者，其先前包含曲妥珠单抗的治疗失败后，按1:1的比例随机接受每3周一次的安贝替单抗30 mg/kg或安慰剂，联合化疗（21天为一个周期，第1天使用紫杉醇175 mg/m2或多西他赛75 mg/m2，或第1天和第8天使用伊立替康125 mg/m2），按联合化疗[紫杉类（紫杉醇或多西他赛）或伊立替康]、HER2表达[免疫组织化学（IHC）3+或IHC 2+/FISH+]和先前治疗线数（1线或≥2线）进行分层。

Primary endpoints were independent review committee-assessed PFS and OS in the intention-to-treatpopulation.

主要终点是独立审查委员会评估的无进展生存期（PFS）和总生存期（OS），在意向治疗人群中进行评估。

This interim analysis was planned when ∼120 PFS events were observed.

此次中期分析计划在观察到约120个无进展生存（PFS）事件时进行。

Results

A total of 188 patients were enrolled and assigned to receive anbenitamab plus chemotherapy (anbenitamab group, n = 95) or chemotherapy alone (control group, n = 93).

共有188名患者被纳入研究，并被分配接受anbenitamab联合化疗（anbenitamab组，n=95）或仅接受化疗（对照组，n=93）。

At the prespecified interim analysis, anbenitamab plus chemotherapy significantly improved PFS [median 7.1 months, 95% confidence interval(CI) 5.5-10.3 months versus 2.7 months, 95% CI 1.5-3.0 months; hazard ratio(HR), 0.25, 95% CI 0.17-0.39, P < 0.0001] and OS (median 19.6 months, 95% CI 15.0 months to not evaluable versus 11.5 months, 95% CI 6.5-14.4 months; HR 0.29, 95% CI 0.17-0.50, P < 0.0001) compared with chemotherapy alone.

在预定的中期分析中，anbenitamab联合化疗显著改善了无进展生存期（PFS）[中位数7.1个月，95%置信区间（CI）5.5-10.3个月，与单独化疗的2.7个月，95% CI 1.5-3.0个月相比；风险比（HR），0.25，95% CI 0.17-0.39，P < 0.0001]和总生存期（OS）（中位数19.6个月，95% CI 15.0个月至无法评估，与单独化疗的11.5个月，95% CI 6.5-14.4个月相比；HR 0.29，95% CI 0.17-0.50，P < 0.0001）。

Grade 3 or higher treatment-related adverse events occurred in 56 (60%) of 94 patients who received anbenitamab plus chemotherapy and 42 (45%) of 93 patients who received chemotherapy alone, with neutropenia (30% versus 22%) and leukopenia (21% versus 25%) being most common.

在94名接受anbenitamab联合化疗的患者中，有56名（60%）出现了3级或更高级别的治疗相关不良事件，而在93名单独接受化疗的患者中，有42名（45%）出现了这些不良事件，其中以中性粒细胞减少症（30%对比22%）和白细胞减少症（21%对比25%）最为常见。

Treatment-related deaths were reported in 0 and 5 patients in the anbenitamab and control groups, respectively.

在anbenitamab组和对照组中，分别有0例和5例患者报告了与治疗相关的死亡。

Conclusions

Compared with chemotherapy alone, anbenitamab plus chemotherapy demonstrated clinically meaningful superior PFS and OS in patients with HER2-positive GC/GEJ adenocarcinoma whose previous therapy containing trastuzumab had failed.

与单纯化疗相比，anbenitamab联合化疗在既往接受过曲妥珠单抗治疗失败的HER2阳性胃癌/胃食管交界处腺癌患者中，显示出具有临床意义的无进展生存期（PFS）和总生存期（OS）的优越性。

These findings warrant confirmation in the final analysis.

这些发现需要在最终分析中得到证实。