Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Haidian District, Beijing, China.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ann Surg Oncol. 2021 Aug;28(8):4413-4422. doi: 10.1245/s10434-020-09405-6. Epub 2021 Jan 3.
Recent studies have reported a beneficial role of trastuzumab in neoadjuvant treatment (NAT) among resectable gastric cancer (GC) patients; however, the effect of adjuvant treatment (AT) combined with trastuzumab is understudied. We performed a retrospective cohort study to compare chemotherapies with or without trastuzumab among human epidermal growth factor receptor 2-positive (HER2 +) locally advanced GC patients in the AT and NAT settings, respectively.
We enrolled 208 HER2 + resected GC patients who underwent perioperative/postoperative treatment in 2010-2019 in a single-centered hospital, including 135 AT patients and 73 NAT patients. We used inverse probability of treatment weighting (IPTW) to balance potential confounding factors between the treatment groups, and estimated the treatment effect of trastuzumab. Pathological and survival outcomes were evaluated.
The number of trastuzumab-exposed patients in the AT and NAT cohorts was 31 (23.0%) and 34 (46.6%), respectively. After IPTW adjustment, AT combined with trastuzumab showed a better overall survival (OS) over chemotherapy alone (p = 0.023). In IPTW-adjusted NAT analysis, trastuzumab-exposed patients had an improvement in tumor pathological regression and downstaging, with lower tumor regression grade scores (p = 0.002), ypTNM stages (p < 0.001), ypN stages (p = 0.035), and ypT stages (p < 0.001). Loss of HER2 positivity following trastuzumab treatment was observed in NAT patients; however, we did not observe any significant effect of trastuzumab on OS (p = 0.126).
Given the improvement in tumor regression and downstaging among NAT patients, and the OS benefit in AT patients, trastuzumab could be considered a promising treatment for locally advanced HER2 + GC patients. In particular, re-evaluation of HER2 status should be considered following NAT combined with trastuzumab.
最近的研究报告称曲妥珠单抗在可切除胃癌（GC）患者的新辅助治疗（NAT）中具有有益作用；然而，曲妥珠单抗辅助治疗（AT）的效果仍研究不足。我们进行了一项回顾性队列研究，分别比较了人表皮生长因子受体 2 阳性（HER2+）局部晚期 GC 患者在 AT 和 NAT 中的曲妥珠单抗联合化疗与单纯化疗。
我们纳入了 2010 年至 2019 年在一家单中心医院接受围手术期/术后治疗的 208 例 HER2+GC 患者，包括 135 例 AT 患者和 73 例 NAT 患者。我们使用逆概率治疗加权（IPTW）来平衡治疗组之间的潜在混杂因素，并估计曲妥珠单抗的治疗效果。评估了病理和生存结果。
AT 和 NAT 队列中接受曲妥珠单抗治疗的患者人数分别为 31 例（23.0%）和 34 例（46.6%）。经过 IPTW 调整后，与单纯化疗相比，AT 联合曲妥珠单抗的总生存（OS）更好（p=0.023）。在 IPTW 调整后的 NAT 分析中，曲妥珠单抗暴露的患者肿瘤病理缓解和降期更好，肿瘤消退分级评分较低（p=0.002），ypTNM 分期（p<0.001）、ypN 分期（p=0.035）和 ypT 分期（p<0.001）。在 NAT 患者中观察到曲妥珠单抗治疗后 HER2 阳性丢失，但我们没有观察到曲妥珠单抗对 OS 的任何显著影响（p=0.126）。
鉴于 NAT 患者肿瘤消退和降期的改善，以及 AT 患者的 OS 获益，曲妥珠单抗可能被认为是局部晚期 HER2+GC 患者的一种有前途的治疗方法。特别是，应考虑在 NAT 联合曲妥珠单抗后重新评估 HER2 状态。
