Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.

Methods

In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy.

在一个开放标签的III期试验中，我们按照1:1:1的比例随机分配了之前未经治疗、中心确认为HER2阳性的晚期胃食管腺癌患者，分别接受Zanidatamab和Tislelizumab联合化疗、Zanidatamab联合化疗或Trastuzumab联合化疗。

The two primary end points were progression-free survivaland overall survival.

两个主要终点是无进展生存期和总生存期。

Results

At a median follow-up of 25.9 months, progression-free survivalwas longer with zanidatamab-tislelizumab-chemotherapy (median among 302 patients, 12.4 months) and zanidatamab-chemotherapy (median among 304 patients, 12.4 months) than with trastuzumab-chemotherapy (median among 308 patients, 8.1 months) (hazard ratiofor progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval{CI}, 0.51 to 0.78]; hazard ratiowith zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons).

在中位随访25.9个月时，zanidatamab-tislelizumab-化疗方案（302名患者中位数，12.4个月）和zanidatamab-化疗方案（304名患者中位数，12.4个月）的无进展生存期比trastuzumab-化疗方案（308名患者中位数，8.1个月）更长（zanidatamab-tislelizumab-化疗方案进展或死亡的风险比为0.63 [95%置信区间{CI}, 0.51至0.78]；zanidatamab-化疗方案的风险比为0.65 [95% CI, 0.52至0.81]；两者比较P<0.001）。

Overall survivalwas longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy (median, 26.4 vs. 19.2 months; hazard ratiofor death, 0.72; 95% CI, 0.57 to 0.90; P = 0.004).

与曲妥珠单抗化疗相比，zanidatamab-tislelizumab-化疗的总生存期更长（中位数，26.4个月对比19.2个月；死亡风险比为0.72；95%置信区间，0.57至0.90；P = 0.004）。

At this interim analysis, overall survivaldid not differ significantly between zanidatamab-chemotherapy (median, 24.4 months) and trastuzumab-chemotherapy (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P = 0.06).

在这次中期分析中，zanidatamab-化疗（中位数，24.4个月）与曲妥珠单抗化疗的总生存期没有显著差异（风险比，0.80；95%置信区间，0.64至1.01；P = 0.06）。

The incidenceof grade 3 or higher adverse events was 83.3% with zanidatamab-tislelizumab-chemotherapy, 73.8% with zanidatamab-chemotherapy, and 74.5% with trastuzumab-chemotherapy; diarrhea was the most common such event, in 24.8%, 20.0%, and 12.9% of patients, respectively.

在接受zanidatamab-tislelizumab-化疗、zanidatamab-化疗和trastuzumab-化疗的患者中，3级或更高级别的不良事件发生率分别为83.3%、73.8%和74.5%；其中，腹泻是最常见的不良事件，分别发生在24.8%、20.0%和12.9%的患者中。

Conclusions

Zanidatamab plus chemotherapy, both with and without tislelizumab, led to longer progression-free survivalthan trastuzumab plus chemotherapy among patients with HER2-positive advanced gastroesophageal adenocarcinoma.

在HER2阳性晚期胃食管腺癌患者中，无论是单用化疗还是联合tislelizumab，zanidatamab加化疗均比trastuzumab加化疗带来了更长的无进展生存期。

At this interim analysis, overall survivalwas longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy; further analyses are planned to assess zanidatamab-chemotherapy.

在这次中期分析中，zanidatamab-tislelizumab-化疗组的总生存期比trastuzumab-化疗组更长；计划进一步分析以评估zanidatamab-化疗。

Diarrhea was a common adverse event.

腹泻是一种常见的不良事件。

(Funded by Jazz Pharmaceuticals and others; HERIZON-GEA-01 ClinicalTrials.gov number, NCT05152147.).

(由 Jazz Pharmaceuticals 等资助; HERIZON-GEA-01 临床试验注册号, NCT05152147.)