Department of Medicine, The University of Chicago Medical Center, Chicago, USA.
Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
ESMO Open. 2022 Feb;7(1):100360. doi: 10.1016/j.esmoop.2021.100360. Epub 2021 Dec 29.
Since completion of the Trastuzumab for Gastric Cancer study, trastuzumab with doublet chemotherapy (a fluoropyrimidine and a platinum) has been the gold-standard first-line therapy for patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-positive (HER2+) gastroesophageal adenocarcinoma (GEA). The safety and efficacy of 23 studies of first-line trastuzumab plus doublet chemotherapy, without checkpoint inhibitors (n = 19) or with checkpoint inhibitors (n = 4), conducted in patients with locally advanced unresectable or metastatic HER2+ GEA, including phase II/III, prospective, and retrospective observational studies, were summarized. In studies without checkpoint inhibitors, the median duration of trastuzumab treatment ranged from 19.5 to 39.0 weeks and from 15.3 to 30.0 weeks for chemotherapy. In studies with checkpoint inhibitors, the median duration of pembrolizumab/trastuzumab/chemotherapy was 30 weeks, and 18 weeks for chemotherapy. In studies without checkpoint inhibitors, treatment-emergent adverse events (TEAEs) of grade ≥3 ranged from 32% to 84%. Serious adverse events (SAEs) ranged from 15% to 39%. Adverse events resulting in discontinuation ranged from 0% to 30%. Treatment-related deaths occurred in 0%-9% of patients. In studies with checkpoint inhibitors, TEAEs of grade ≥3 were 57%. SAEs ranged from 31% to 38%. Adverse events resulting in discontinuation ranged from 5% to 24%. Treatment-related deaths occurred in 0%-3% of patients. In studies without checkpoint inhibitors, objective response rate (ORR) ranged from 39% to 82%, median progression-free survival (PFS) from 5.7 to 11.6 months, and median overall survival (OS) from 11.2 to 27.6 months. In studies with checkpoint inhibitors, ORR ranged from 39% to 86%, median PFS from 8.0 to 13.0 months, and median OS from 19.3 to 27.3 months. This review provides a historical benchmark on safety and efficacy of available first-line chemotherapy-based standard of care for patients with locally advanced unresectable or metastatic HER2+ GEA.
自曲妥珠单抗治疗胃癌研究完成以来，曲妥珠单抗联合双药化疗（一种氟嘧啶类药物和一种铂类药物）已成为局部晚期不可切除或转移性人表皮生长因子受体 2 阳性（HER2+）胃食管腺癌（GEA）患者的一线治疗金标准。对 23 项曲妥珠单抗联合双药化疗一线治疗局部晚期不可切除或转移性 HER2+GEA 患者的安全性和有效性的研究进行了总结，这些研究包括 II/III 期前瞻性和回顾性观察性研究，其中无检查点抑制剂（n=19）或有检查点抑制剂（n=4）。在无检查点抑制剂的研究中，曲妥珠单抗治疗的中位持续时间为 19.5 至 39.0 周，化疗的中位持续时间为 15.3 至 30.0 周。在有检查点抑制剂的研究中，帕博利珠单抗/曲妥珠单抗/化疗的中位持续时间为 30 周，化疗的中位持续时间为 18 周。在无检查点抑制剂的研究中，≥3 级治疗相关不良事件（TEAE）发生率为 32%至 84%。严重不良事件（SAE）发生率为 15%至 39%。导致停药的不良事件发生率为 0%至 30%。治疗相关死亡发生在 0%至 9%的患者中。在有检查点抑制剂的研究中，≥3 级的 TEAE 发生率为 57%。SAE 发生率为 31%至 38%。导致停药的不良事件发生率为 5%至 24%。治疗相关死亡发生在 0%至 3%的患者中。在无检查点抑制剂的研究中，客观缓解率（ORR）为 39%至 82%，中位无进展生存期（PFS）为 5.7 至 11.6 个月，中位总生存期（OS）为 11.2 至 27.6 个月。在有检查点抑制剂的研究中，ORR 为 39%至 86%，中位 PFS 为 8.0 至 13.0 个月，中位 OS 为 19.3 至 27.3 个月。本综述为局部晚期不可切除或转移性 HER2+GEA 患者现有基于化疗的一线标准治疗的安全性和疗效提供了历史基准。
