Peng Zhi, Zhang Xiaotian, Liang Han, Zheng Zhichao, Wang Zhenning, Liu Hao, Hu Jiankun, Sun Yihong, Zhang Yanqiao, Yan Han, Tong Lin, Xu Jiahui, Ji Jiafu, Shen Lin
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
JAMA Oncol. 2025 Apr 17. doi: 10.1001/jamaoncol.2025.0522.
Effective treatment of locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer remains a challenge.
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.
DESIGN, SETTING, AND PARTICIPANTS: This was an open-label phase 2 randomized clinical trial conducted at 8 study sites in China. Patient recruitment started on February 25, 2021, and this study is ongoing as participants are still being actively followed up. Chinese patients eligible for surgery with locally advanced ERBB2-positive GC or adenocarcinoma of the GEJ were included. Data were analyzed from March 2021 to October 2023.
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.
The primary efficacy end point was the pathological complete response (pCR) rate following completion of neoadjuvant therapy and surgery.
In total, 42 patients were screened and randomly assigned to arm A (n = 21) or arm B (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. 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). Age younger than 65 years, male sex, and intestinal Lauren classification were significantly associated with a better pCR rate in arm A. Median event-free survival, disease-free survival, and overall survival were not reached. 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. The incidence of 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.
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.
ClinicalTrials.gov Identifier: NCT04661150.
局部晚期胃癌（GC）或胃食管交界（GEJ）癌的有效治疗仍然是一项挑战。
比较阿替利珠单抗联合曲妥珠单抗加卡培他滨和奥沙利铂化疗（XELOX）与曲妥珠单抗加XELOX在中国局部晚期人表皮生长因子受体2（ERBB2；原HER2）阳性GC或GEJ腺癌患者中的疗效和安全性。
设计、地点和参与者：这是一项在中国8个研究地点进行的开放标签2期随机临床试验。患者招募于2021年2月25日开始，由于仍在对参与者进行积极随访，本研究正在进行中。纳入了符合手术条件的局部晚期ERBB2阳性GC或GEJ腺癌的中国患者。对2021年3月至2023年10月的数据进行了分析。
符合条件的患者被纳入并按1:1随机分配接受围手术期治疗，即阿替利珠单抗联合曲妥珠单抗加XELOX（A组）或曲妥珠单抗加XELOX（B组），进行3个新辅助周期（每个周期3周）和5个辅助周期。
主要疗效终点是新辅助治疗和手术后的病理完全缓解（pCR）率。
总共筛选了42例患者并随机分配至A组（n = 21）或B组（n = 21）。A组和B组的中位（范围）年龄分别为61（33 - 72）岁和65（49 - 72）岁，39例患者（93%）为男性。A组的pCR率（8例[38%]）显著高于B组（3例[14%]；差异为23.8%；90%CI，1.3 - 44.7）。年龄小于65岁、男性以及肠型劳伦分类与A组更好的pCR率显著相关。中位无事件生存期、无病生存期和总生存期均未达到。基于相同的解释方式，主要病理缓解在两组之间应具有统计学显著差异，而其他结局指标仍无显著差异。治疗中出现的不良事件发生率在A组和B组分别为100%（21例中的21例）和100%（21例中的21例）；3级或更高等级的治疗中出现的不良事件分别为57%（21例中的12例）和67%（21例中的14例）；严重治疗中出现的不良事件分别为29%（21例中的6例）和10%（21例中的2例）。
在这项随机临床试验中，在曲妥珠单抗加XELOX治疗中添加阿替利珠单抗在该患者群体中显示出有前景的疗效，且未引发新的安全担忧。
ClinicalTrials.gov标识符：NCT04661150。
