Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka; and Cancer Center, Gifu University Hospital, Gifu, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
J Clin Oncol. 2020 Jun 10;38(17):1919-1927. doi: 10.1200/JCO.19.03077. Epub 2020 Mar 24.
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 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/m, 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.
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; = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively ( = 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.
The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.
本研究评估了曲妥珠单抗在人表皮生长因子受体 2（HER2）阳性晚期胃或胃食管交界处（G/GEJ）癌患者中的持续应用（TBP）。
符合条件的患者为 HER2 阳性晚期 G/GEJ 癌患者，对一线化疗联合曲妥珠单抗、氟嘧啶和铂类药物治疗耐药。患者被随机分配至紫杉醇（80mg/m2，第 1、8 和 15 天，每 4 周）或紫杉醇联合曲妥珠单抗（PT；初始剂量 8mg/kg，然后 6mg/kg，每 3 周）组。主要终点是无进展生存期（PFS）。次要终点包括总生存期（OS）、缓解率和安全性。分析了一线治疗后肿瘤组织中 HER2 表达状态、血清游离 DNA 中 HER2 扩增以及可溶性 HER2 水平等生物标志物。
共有 91 例患者被分配至紫杉醇（n=46）和 PT（n=45）组。紫杉醇组和 PT 组的中位 PFS 分别为 3.2 个月和 3.7 个月（风险比 [HR]，0.91；95%CI，0.67 至 1.22；P=0.33），两组的中位 OS 均为 10 个月（HR，1.2；95%CI，0.75 至 2.0；P=0.20）。紫杉醇组和 PT 组的总缓解率分别为 32%和 33%（P=1.00），两组安全性相当。探索性分析显示，16 例可评估肿瘤组织的患者中，有 11 例（69%）在一线化疗后失去了肿瘤组织的 HER2 阳性，68 例患者中有 41 例（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。
TBP 策略未能改善 HER2 阳性晚期 G/GEJ 癌症患者的 PFS，也未发现有益的生物标志物。
