曲妥珠单抗德鲁替康与戈沙妥珠单抗在HER2阴性转移性乳腺癌中的比较：一项大型真实世界数据分析。
Comparison of trastuzumab deruxtecan and sacituzumab govitecan in HER2-negative metastatic breast cancer: a large real-world data analysis.
作者信息
Sledge George W Jr, Xiu Joanne, Solzak Jeffrey Peter, Ribeiro Jennifer, Mahtani Reshma L, Lustberg Maryam B, Oberley Matthew J, Radovich Milan, Spetzler David
机构信息
Caris Life Sciences, 4610 S 44th Pl, Phoenix, AZ, 85040, USA.
Baptist Health Miami Cancer Institute, Miami, FL, 33176, USA.
出版信息
Breast Cancer Res. 2025 Aug 11;27(1):144. doi: 10.1186/s13058-025-02094-7.
BACKGROUND
Trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) are antibody-drug conjugates (ADCs) increasingly used in HER2-negative breast cancer. We hypothesized that treatment benefit would vary across HER2-null, HER2-ultra-low, and HER2-low subgroups of HER2-negative breast cancer patients. We also aimed to study the clinical impact of different sequencing of the two ADCs.
METHODS
We analyzed a large, real-world cohort of 4,030 HER2-negative breast cancer specimens from patients treated with T-DXd or SG. Tumors underwent molecular profiling including HER2 status (IHC, CISH) and hormone receptor (HR) status (IHC) at Caris Life Sciences (Phoenix, AZ, USA). Real-world clinical data were obtained from insurance claims and analyzed by Cox proportional hazards.
RESULTS
HER2-low, HER2-ultra-low, and HER2-null cohorts treated with T-DXd had decreasing time-on-treatment (TOT; 4.8, 4.1, and 3.5 mo., respectively, < 0.001), while HER2 status had little impact on SG TOT (3.0, 2.8, and 3.4 mo., respectively). Patients with HR+/HER2-negative tumors showed longer TOT when treated with T-DXd only ( = 1,049) than with SG-only ( = 453), even in the HER2-null subset ( < 0.001). In all HER2-negative patients treated with both ADCs, T-DXd-first ( = 547) or SG-first ( = 432) showed no cumulative TOT difference (10.4 vs. 10.8 mo., = 0.356); however, the HER2-null subset showed preference for SG-first and this was restricted to the HR- subset [TOT: 11.7 vs. 7.4 mo., hazard ratio = 0.478 (95% CI: 0.333–0.685), < 0.0001; OS: 19.7 vs. 11.8 mo., hazard ratio = 0.478 (95% CI: 0.303–0.756)].
CONCLUSIONS
Analysis of this large real-world dataset allowed interrogation of T-DXd and SG benefit and treatment sequencing across HER2-negative subsets, providing important clinical insights into two widely used ADCs in breast cancer. We demonstrate improved relative outcomes associated with T-DXd in HR+ tumors across all HER2-negative subgroups and comparable benefit of the two ADCs in TNBC. Sequencing preference was seen in HR−/HER2-null patients only, favoring SG-first for TOT and OS. These findings warrant further validation in independent cohorts.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1186/s13058-025-02094-7.
背景
曲妥珠单抗德鲁昔单抗（T-DXd）和戈沙妥珠单抗（SG）是越来越多地用于治疗人表皮生长因子受体2（HER2）阴性乳腺癌的抗体偶联药物（ADC）。我们推测，HER2阴性乳腺癌患者的治疗获益在HER2缺失、HER2超低表达和HER2低表达亚组中会有所不同。我们还旨在研究这两种ADC不同给药顺序的临床影响。
方法
我们分析了来自接受T-DXd或SG治疗的患者的4030例HER2阴性乳腺癌标本的大型真实世界队列。肿瘤在美国卡里生命科学公司（亚利桑那州凤凰城）进行了分子分析，包括HER2状态（免疫组化、原位杂交）和激素受体（HR）状态（免疫组化）。从保险理赔中获取真实世界临床数据，并通过Cox比例风险模型进行分析。
结果
接受T-DXd治疗的HER2低表达、HER2超低表达和HER2缺失队列的治疗持续时间（TOT）逐渐缩短（分别为4.8、4.1和3.5个月，P<0.001），而HER2状态对SG的TOT影响较小（分别为3.0、2.8和3.4个月）。HR阳性/HER2阴性肿瘤患者仅接受T-DXd治疗（n=1049）时的TOT比仅接受SG治疗（n=453）时更长，即使在HER2缺失亚组中也是如此（P<0.001）。在所有接受两种ADC治疗的HER2阴性患者中，先使用T-DXd（n=547）或先使用SG（n=432）的累积TOT无差异（10.4个月对10.8个月，P=0.356）；然而，HER2缺失亚组表现出先使用SG的偏好，且这仅限于HR阴性亚组（TOT：11.7个月对7.4个月，风险比=0.478（95%CI：0.333–0.685），P<0.0001；总生存期（OS）：19.7个月对11.8个月，风险比=0.478（95%CI：0.303–0.756））。
结论
对这个大型真实世界数据集的分析使得能够探究T-DXd和SG在HER2阴性亚组中的获益情况及治疗顺序，为乳腺癌中两种广泛使用的ADC提供了重要的临床见解。我们证明在所有HER2阴性亚组的HR阳性肿瘤中，T-DXd相关的相对结局有所改善，在三阴性乳腺癌中两种ADC的获益相当。仅在HR阴性/HER2缺失患者中观察到给药顺序偏好，在TOT和OS方面更倾向于先使用SG。这些发现需要在独立队列中进一步验证。
补充信息
在线版本包含可在10.1186/s13058-025-02094-7获取的补充材料。
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