Oaknin Ana, Lee Jung-Yun, Makker Vicky, Oh Do-Youn, Banerjee Susana, González-Martín Antonio, Jung Kyung Hae, Ługowska Iwona, Manso Luis, Manzano Aránzazu, Melichar Bohuslav, Siena Salvatore, Stroyakovskiy Daniil, Fielding Anitra, Puvvada Soham, Smith Ann, Meric-Bernstam Funda
Medical Oncology Service, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Department of Obstetrics and Gynecology, Yonsei Cancer Center and Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Adv Ther. 2025 May;42(5):2015-2018. doi: 10.1007/s12325-024-03080-9. Epub 2025 Mar 6.
of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects were seen in people with the highest tumor level of HER2 [defined as immunohistochemistry (IHC) 3+]. In this previous analysis, the HER2 expression was measured at a central laboratory. In clinical practice, HER2 expression will likely be measured at a local laboratory, so understanding whether T-DXd has similar effects regardless of how HER2 expression is measured is important. Here, we looked at the effects of T-DXd based on the HER2 test result used to determine a person's eligibility for the study, which could be measured using a local or central laboratory. In people with IHC 3+ tumors (where HER2 was measured at a local or central laboratory), 51% had a decrease in the size or number of tumors, according to established criteria (referred to as an objective response), while, in people with IHC 2+ tumors, 26% had an objective response. Side effects with T-DXd were consistent with previous studies. These results confirm T-DXd has antitumor effects in HER2-expressing cancers where the HER2 expression is measured by a local or central laboratory.
原文《通过入组时HER2免疫组化状态分析曲妥珠单抗德鲁替康在HER2表达实体瘤中的疗效:DESTINY-PanTumor02的事后分析》。曲妥珠单抗德鲁替康(T-DXd)是一种抗体药物偶联物,它是一种化疗药物,由连接子(德鲁替康)与抗体(曲妥珠单抗)连接而成。曲妥珠单抗与癌细胞上的人表皮生长因子受体2(HER2)蛋白结合,在那里释放化疗药物以杀死这些细胞。DESTINY-PanTumor02临床研究测试了T-DXd对各种HER2表达癌症患者的有效性以及治疗的安全性。DESTINY-PanTumor02之前的结果表明,T-DXd具有抗肿瘤活性,在HER2肿瘤水平最高的患者(定义为免疫组化(IHC)3+)中观察到的效果最为显著。在之前的这项分析中,HER2表达是在中央实验室测量的。在临床实践中,HER2表达可能会在当地实验室测量,因此了解无论HER2表达如何测量T-DXd是否具有相似的效果很重要。在这里,我们根据用于确定患者是否符合研究入组条件的HER2检测结果来观察T-DXd的效果,该检测结果可以在当地或中央实验室进行测量。在IHC 3+肿瘤患者(HER2在当地或中央实验室测量)中,根据既定标准(称为客观缓解),51%的患者肿瘤大小或数量有所减少,而在IHC 2+肿瘤患者中,26%的患者有客观缓解。T-DXd的副作用与之前的研究一致。这些结果证实,在通过当地或中央实验室测量HER2表达的HER2表达癌症中,T-DXd具有抗肿瘤作用。