Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan.
Cancer Discov. 2020 May;10(5):688-701. doi: 10.1158/2159-8290.CD-19-1014. Epub 2020 Mar 25.
HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or -mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8-11.1] months. In -mutant non-small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1-14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and -mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors. SIGNIFICANCE: T-DXd demonstrated promising activity in a heterogeneous patient population with heavily pretreated HER2-expressing or -mutant solid tumors, especially -mutant NSCLC. The safety profile was generally acceptable. Interstitial lung disease can be severe and requires prompt monitoring and intervention. Further research of T-DXd is warranted to address these unmet medical needs...
曲妥珠单抗-德鲁替康（T-DXd）在既往治疗、HER2 过表达（免疫组化≥1+）、非乳腺/非胃或非突变的实体瘤患者中的安全性/耐受性和活性评估：一项 I 期临床试验的 60 例患者结果（NCT02564900）。最常见（>50%）的治疗后出现的不良事件（TEAE）是恶心、食欲下降和呕吐。有 2 例与药物相关的 TEAEs 与致死结局相关。确认的客观缓解率（ORR）为 28.3%（17/60）。中位无进展生存期（PFS）为 7.2 个月[95%置信区间（CI），4.8-11.1]。在 -突变非小细胞肺癌（NSCLC）中，ORR 为 72.7%（8/11），中位 PFS 为 11.3 个月（95%CI，8.1-14.3）。在包括 HER2 过表达 NSCLC、结直肠癌、唾液腺癌、胆管癌、子宫内膜癌和 -突变 NSCLC 和乳腺癌在内的 6 种肿瘤类型中观察到确认的缓解。结果表明 T-DXd 对 HER2 过表达/突变的实体瘤具有治疗潜力。意义：T-DXd 在既往治疗、HER2 过表达或 -突变的实体瘤的异质性患者群体中显示出有前景的活性，特别是 -突变 NSCLC。安全性概况通常可以接受。间质性肺病可能很严重，需要及时监测和干预。需要进一步研究 T-DXd，以解决这些未满足的医疗需求。
