Atezolizumab and Trastuzumab Plus Chemotherapy for ERBB2-Positive Locally Advanced Resectable Gastric Cancer: A Randomized Clinical Trial.

Background

To compare the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin chemotherapy (XELOX) vs trastuzumab plus XELOX in Chinese patients with locally advanced human epidermal growth factor receptor 2 (ERBB2; formerly HER2)-positive GC or adenocarcinoma of the GEJ.

比较阿替利珠单抗联合曲妥珠单抗联合卡培他滨和奥沙利铂化疗（XELOX）与曲妥珠单抗联合XELOX在中国局部晚期人类表皮生长因子受体2（ERBB2；前称HER2）阳性GC或GEJ腺癌患者中的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: This was an open-label phase 2 randomized clinical trial conducted at 8 study sites in China.

这是一项在中国8个研究地点进行的开放标签二期随机临床试验。

Patient recruitment started on February 25, 2021, and this study is ongoing as participants are still being actively followed up.

患者招募始于2021年2月25日，目前该研究仍在进行中，因为参与者仍在积极随访中。

Chinese patients eligible for surgery with locally advanced ERBB2-positive GC or adenocarcinoma of the GEJ were included.

纳入了符合手术条件的中国局部晚期ERBB2阳性胃癌或胃食管交界处腺癌患者。

Data were analyzed from March 2021 to October 2023.

数据从2021年3月分析至2023年10月。

Methods

Eligible patients were enrolled and randomly assigned 1:1 to perioperative treatment with either atezolizumab plus trastuzumab plus XELOX (arm A) or trastuzumab plus XELOX (arm B) for 3 neoadjuvant cycles (3 weeks per cycle) and 5 adjuvant cycles.

符合条件的患者被纳入研究，并按1:1的比例随机分配接受围手术期治疗，治疗方案为：A组使用阿替利珠单抗加曲妥珠单抗加XELOX方案，B组使用曲妥珠单抗加XELOX方案，每3周为一个周期，共进行3个新辅助治疗周期和5个辅助治疗周期。

main_outcomes_and_measures

The primary efficacy end point was the pathological complete response (pCR) rate following completion of neoadjuvant therapy and surgery.

主要疗效终点是完成新辅助治疗和手术后的病理完全缓解（pCR）率。

Results

In total, 42 patients were screened and randomly assigned to arm A (n = 21) or arm B (n = 21).

共有42名患者接受了筛查，并随机分配到A组（n = 21）或B组（n = 21）。

The median (range) ages were 61 (33-72) years and 65 (49-72) years in arm A and arm B, respectively, and 39 patients (93%) were male.

A组和B组的中位年龄分别为61（33-72）岁和65（49-72）岁，39名患者（93%）为男性。

The pCR rate was significantly higher in arm A (8 [38%]) than arm B (3 [14%]; difference, 23.8%; 90% CI, 1.3-44.7).

在A组中，pCR率显著高于B组（A组8例[38%]，B组3例[14%]；差异为23.8%，90%置信区间为1.3-44.7）。

Age younger than 65 years, male sex, and intestinal Lauren classification were significantly associated with a better pCR rate in arm A.

年龄小于65岁、男性以及肠型Lauren分类与A组更好的pCR率显著相关。

Median event-free survival, disease-free survival, and overall survivalwere not reached.

中位无事件生存期、无病生存期和总生存期均未达到。

Based on the same way of interpretation, major pathologic response should be statistically significantly different between the 2 arms, while other outcome measures remained not significantly different.

基于相同的解释方式，主要病理反应在两组间应有统计学上的显著差异，而其他结果指标保持无显著差异。

The incidenceof treatment-emergent adverse events was 100% (21 of 21) and 100% (21 of 21) in arms A and B, respectively; grade 3 or higher TEAEs, 57% (12 of 21) and 67% (14 of 21), respectively; and serious TEAEs, 29% (6 of 21) and 10% (2 of 21), respectively.

治疗相关不良事件的发生率为100%（21/21）和100%（21/21），分别在A组和B组；3级或更高级别的TEAEs分别为57%（12/21）和67%（14/21）；严重TEAEs分别为29%（6/21）和10%（2/21）。

conclusions_and_relevance

In this randomized clinical trial, add-on atezolizumab to trastuzumab plus XELOX therapy demonstrated promising efficacy in this patient population, and no new safety concerns were raised.

在这项随机临床试验中，将阿替利珠单抗添加到曲妥珠单抗加XELOX治疗中，在这一患者群体中显示出有希望的疗效，且未引发新的安全问题。

trial_registration

ClinicalTrials.gov Identifier: NCT04661150.

临床试验注册号：NCT04661150。