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PURPOSE

To investigate efficacy and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

METHODS

Patients with locally advanced or metastatic HER2-low (cohort 1, immunohistochemistry 2+/in situ hybridization-negative; cohort 2, immunohistochemistry 1+) gastric/GEJ adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive, received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate by independent central review.

RESULTS

Among 21 patients enrolled in cohort 1 and 24 enrolled in cohort 2, 19 and 21 patients, respectively, had central HER2 confirmation, received T-DXd, and had measurable tumors at baseline. The confirmed objective response rate was 26.3% (95% CI, 9.1 to 51.2) from five partial responses in cohort 1 and 9.5% (95% CI, 1.2 to 30.4) from two partial responses in cohort 2. Thirteen patients (68.4%) in cohort 1 and 12 (60.0%) in cohort 2 experienced reduced tumor size. The median overall survival was 7.8 months (95% CI, 4.7 to nonevaluable) in cohort 1 and 8.5 months (95% CI, 4.3 to 10.9) in cohort 2; the median progression-free survival was 4.4 months (95% CI, 2.7 to 7.1) and 2.8 months (95% CI, 1.5 to 4.3), respectively. The most common grade ≥ 3 treatment-emergent adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Drug-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 or 2). No drug-related deaths occurred.

CONCLUSION

This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/GEJ adenocarcinoma.

目的

研究曲妥珠单抗 deruxtecan（T-DXd）在人表皮生长因子受体 2（HER2）低表达胃或胃食管交界处（GEJ）腺癌中的疗效和安全性。

方法

接受过至少两种包括氟嘧啶和铂类药物在内的既往治疗方案，但无抗 HER2 治疗史的局部晚期或转移性 HER2 低表达（队列 1，免疫组化 2+/原位杂交阴性；队列 2，免疫组化 1+）胃/GEJ 腺癌患者，接受 T-DXd 6.4mg/kg 静脉输注，每 3 周一次。主要终点是独立中心评估确认的客观缓解率。

结果

队列 1 纳入 21 例患者，队列 2 纳入 24 例患者，分别有 19 例和 21 例患者经中心 HER2 确证，接受 T-DXd 治疗且基线时存在可测量肿瘤。队列 1 中有 5 例部分缓解，确认的客观缓解率为 26.3%（95%CI，9.1 至 51.2）；队列 2 中有 2 例部分缓解，确认的客观缓解率为 9.5%（95%CI，1.2 至 30.4）。队列 1 中有 13 例（68.4%）患者和队列 2 中有 12 例（60.0%）患者的肿瘤大小缩小。队列 1 的中位总生存期为 7.8 个月（95%CI，4.7 至无法评估），队列 2 为 8.5 个月（95%CI，4.3 至 10.9）；中位无进展生存期分别为 4.4 个月（95%CI，2.7 至 7.1）和 2.8 个月（95%CI，1.5 至 4.3）。队列 1 和队列 2 中最常见的≥3 级治疗相关不良事件是贫血（30.0%和 29.2%）、中性粒细胞计数减少（25.0%和 29.2%）和食欲下降（20.0%和 20.8%）。各队列中均有 1 例患者发生 1 级或 2 级药物相关间质性肺病/肺炎。无药物相关死亡事件发生。