Nozawa K, Iwata H, Mukohara T, Taira T, Yoshimura A, Nagai S E, Hashimoto J, Matsuura K, Mizuno T, Shinden Y, Yamamoto M, Takano T, Wakahara M, Terakawa H, Yamanaka T, Kojima Y, Nakayama T, Hirakawa Y, Kuge K, Tanabe A, Tsurutani J
Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan; Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
ESMO Open. 2025 Jul 25;10(8):105511. doi: 10.1016/j.esmoop.2025.105511.
Trastuzumab deruxtecan (T-DXd) is recommended in the second-line or later setting for patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer (mBC). However, clinical evidence for optimal post-T-DXd treatment is lacking. The EN-SEMBLE study examined the distribution of post-T-DXd treatment regimens, their effectiveness, and the incidence of interstitial lung disease (ILD) in the real-world setting.
EN-SEMBLE was a real-world, observational, cohort study conducted nationwide in Japan. Patients with HER2-positive mBC who received T-DXd between 25 May 2020 and 30 November 2021 and started another treatment regimen after T-DXd discontinuation were eligible for inclusion. Study outcomes included the distribution of the first post-T-DXd treatments; effectiveness outcomes including real-world progression-free survival (rwPFS) and overall survival (OS); incidence of ILD; and outcomes by patient and treatment characteristics.
The analysis included 664 patients. The first post-T-DXd treatment was another anti-HER2 therapy in 486/664 patients. This included anti-HER2 antibodies in 361/664 patients, and HER2-tyrosine kinase inhibitors (TKIs) in 113/664 patients. The median first post-T-DXd rwPFS was 4.1 months [95% confidence interval (CI) 3.9-4.5 months], and the median OS was 16.2 months (95% CI 13.8-17.2 months). Outcomes were similar with anti-HER2 antibodies and HER2-TKIs. The rwPFS and OS were numerically longer in patients who discontinued T-DXd due to adverse events (AEs), including ILD, and in patients who had a complete or partial response to T-DXd. The ILD recurrence/exacerbation rate was 3.2% during the first post-T-DXd treatment.
Sequential HER2-targeted therapy as the first post-T-DXd treatment in HER2-positive mBC was feasible and demonstrated clinical benefit, particularly in patients who discontinued T-DXd treatment due to AEs and those who achieved a response to T-DXd. Patients who developed ILD during T-DXd treatment had a low risk of recurrence/exacerbation in subsequent therapy.
曲妥珠单抗德鲁替康（T-DXd）被推荐用于人表皮生长因子受体2（HER2）阳性复发或转移性乳腺癌（mBC）患者的二线或更晚期治疗。然而，缺乏关于T-DXd治疗后最佳治疗方案的临床证据。EN-SEMBLE研究在真实世界环境中考察了T-DXd治疗后方案的分布、其有效性以及间质性肺病（ILD）的发生率。
EN-SEMBLE是一项在日本全国范围内开展的真实世界观察性队列研究。2020年5月25日至2021年11月30日期间接受T-DXd治疗且在T-DXd停药后开始另一种治疗方案的HER2阳性mBC患者符合纳入条件。研究结果包括首个T-DXd治疗后治疗方案的分布；有效性结果，包括真实世界无进展生存期（rwPFS）和总生存期（OS）；ILD的发生率；以及按患者和治疗特征划分的结果。
分析纳入了664例患者。664例患者中有486例在首个T-DXd治疗后接受了另一种抗HER2治疗。其中361例患者接受了抗HER2抗体治疗，113例患者接受了HER2酪氨酸激酶抑制剂（TKI）治疗。首个T-DXd治疗后的rwPFS中位数为4.1个月[95%置信区间（CI）3.9 - 4.5个月]，OS中位数为16.2个月（95% CI 13.8 - 17.2个月）。抗HER2抗体和HER2-TKI的治疗结果相似。因不良事件（AE）（包括ILD）而停用T-DXd的患者以及对T-DXd有完全或部分缓解的患者，其rwPFS和OS在数值上更长。首个T-DXd治疗期间ILD复发/加重率为3.2%。
在HER2阳性mBC中，序贯HER2靶向治疗作为首个T-DXd治疗后治疗方案是可行的，并显示出临床获益，特别是在因AE而停用T-DXd治疗的患者以及对T-DXd有反应的患者中。在T-DXd治疗期间发生ILD的患者在后续治疗中复发/加重风险较低。
