Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, Rome, Italy.
Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, Italy.
Oncologist. 2024 Apr 4;29(4):303-310. doi: 10.1093/oncolo/oyad308.
Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population.
Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally. Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis. The primary endpoint was real-word PFS (rwPFS).
One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%). T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd. With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; P = .098). Any-grade toxicity was registered in 84 patients (59%). Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients' response and survival outcomes.
Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.
曲妥珠单抗-德鲁替康（T-DXd）在预处理过的 HER2+转移性乳腺癌（mBC）患者中显示出前所未有的疗效。然而，关于其在常规临床实践中的疗效的数据很少。在这项多中心回顾性研究中，我们研究了 T-DXd 在真实人群中的疗效和安全性。
从 12 家意大利医院收集了接受 T-DXd 治疗的 HER2+mBC 患者的临床病理信息。HER2 状态由当地确定。分析纳入了至少接受一次 T-DXd 治疗的患者，无论其是否为晚期疾病的任何治疗线。主要终点是真实世界无进展生存期（rwPFS）。
共纳入 143 例患者。中位年龄为 66 岁（范围：37-90 岁），4 例为男性。108 例（75%）患者的激素受体（HR）状态为阳性，35 例（25%）为阴性。T-DXd 分别作为一线、二线、三线和后续线治疗的患者分别为 4 例（3%）、16 例（11%）、42 例（29%）和 81 例（57%）。在 123 例可测量疾病患者中，ORR 为 68%，DCR 为 93%（9 例 CR，74 例 PR，30 例 SD）。9 例（7%）患者对 T-DXd 具有原发性耐药性。中位随访 12 个月时，中位 rwPFS 为 16 个月。6、12 和 18 个月时的 rwPFS 分别为 84%、59%和 39%。在接受 T-DXd 作为一线/二线治疗的患者与进一步治疗线的患者之间，rwPFS 有较好的趋势（17 个月 vs. 15 个月；P=0.098）。84 例（59%）患者出现任何级别的毒性。报告的最常见不良反应（AE）为恶心（33%）、中性粒细胞减少（21%）和乏力（21%）。肝毒性和腹泻少见（分别为 5%和 1%）。18%的患者出现严重毒性，最常见的为中性粒细胞减少、恶心/呕吐和ILD，分别为 15、2 和 3 例。37 例（26%）患者因 AE 而减少剂量。剂量减少和 AE 不影响患者的反应和生存结局。
在未经选择的 HER2+mBC 真实人群中，T-DXd 的疗效和安全性得到了证实。这些结果与已知发现一致，且未报告新的安全性问题。
