PURPOSE This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively (P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.

中文翻译：

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曲妥珠单抗在 HER2 阳性晚期胃癌或胃食管交界处癌患者中超过进展的随机 II 期研究：WJOG7112G（T-ACT 研究）

目的 本研究评估了曲妥珠单抗在进展期 (TBP) 后在人表皮生长因子受体 2 (HER2) 阳性晚期胃癌或胃食管交界处 (G/GEJ) 癌中的持续使用。患者和方法 曲妥珠单抗联合氟嘧啶和铂类一线化疗无效的 HER2 阳性晚期 G/GEJ 癌症患者符合条件。患者被随机分配到紫杉醇组（80 mg/m2，第 1、8 和 15 天，每 4 周一次）或紫杉醇联合曲妥珠单抗（PT；最初为 8 mg/kg，随后为 6 mg/kg，每 3 周一次）组。主要终点是无进展生存期（PFS）。次要终点包括总生存期 (OS)、反应率和安全性。一线治疗后肿瘤组织中HER2表达状态等生物标志物，对血清无细胞 DNA 中的 HER2 扩增进行了评估，并对可溶性 HER2 水平进行了分析。结果 总的来说，91 名患者被分配到紫杉醇（n = 46）和 PT（n = 45）组。紫杉醇组和 PT 组的中位 PFS 分别为 3.2 和 3.7 个月（风险比 [HR]，0.91；80% CI，0.67 至 1.22；P = .33），两组的中位 OS 均为 10 个月（ HR，1.2；95% CI，0.75 至 2.0；P = .20）。紫杉醇和 PT 组的总体反应率分别为 32% 和 33% (P = 1.00)，并且两组之间的安全性相当。在探索性分析中，16 名肿瘤组织可用的患者中有 11 名（69%）在一线化疗后肿瘤组织的 HER2 阳性消失，并且在 68 名患者中的 41 名（60%）检测到循环 HER2 DNA 扩增。然而，未发现与 TBP 疗效相关的生物标志物。结论 TBP 策略未能改善 HER2 阳性晚期 G/GEJ 癌患者的 PFS，并且未发现有益的生物标志物。