Antibody–drug conjugate sequencing in HER2-positive metastatic breast cancer: Real-world outcomes of trastuzumab deruxtecan with and without prior T-DM1 exposure
Makaleler > Tam Makale · 2026
Yazarlar: Fatih Kemik, Taha Koray Şahin, Hakan Özçelik, Ahmet Sezer, Gül Başaran, Sakine Damla Açıkel Yüksel, Gizem Güney, İbrahim Yıldız, Özlem Er, Taner Korkmaz, Sedat Biter, Dilek Erdem, Salih Tünbekici, Ahmet Oruç, Ali Kaan Güren, Kerim Kaban, Musa Barış Aykan, Ömer Burak Ekinci, İlknur Deliktaş Onur, Ali Kalem, Oğuz Altunok, Mustafa Seyyar, Bünyamin Güney, Orhun Akdoğan, Melike Yazıcı, Nargiz Majidova, Sema Türker, Bahadır Köylü, Cevat İlteriş Kıkılı, Nazan Demir, Didem Tunalı, Şahin Laçin, Deniz Tural, Ahmet Bilici, Ertuğrul Bayram, Erdem Göker, Murat Araz, İbrahim Vedat Bayoğlu, Nil Molinas Mandel, Nuri Karadurmuş, Emir Çelik, Öztürk Ateş, Havva Yeşil Çınkır, Mesut Yılmaz, Rıza Umar Gürsu, Ozan Yazıcı, Devrim Çabuk, Deniz Can Güven, Fatih Selçukbiricik, Sercan Aksoy, Şeyda Gündüz
The Breast, Uluslararası, Wos, 2026, cilt 87, ss 104785-104785
DOI: 10.1016/j.breast.2026.104785
Özet
BACKGROUND: Optimal sequencing of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer (mBC) remains uncertain, and real-world evidence on the impact of prior T-DM1 exposure on subsequent T-DXd outcomes is limited. METHODS: We conducted a multicenter, retrospective cohort study across 21 oncology centers in Türkiye including consecutive adults with HER2 positive mBC who received at least one cycle of T-DXd between 2020 and 2025. Patients were classified as T-DM1 pretreated or T-DM1 naive at T-DXd initiation. The primary endpoint was progression free survival (PFS); secondary endpoints included objective response rate (ORR), duration of response (DOR), and overall survival (OS). To address confounding by indication, we applied stabilized inverse probability of treatment weighting (IPTW) based on prespecified clinical covariates and assessed covariate balance using standardized mean differences. RESULTS: Among 218 patients treated with T-DXd, 137 (62.8%) had received prior T-DM1 and 81 (37.2%) were T-DM1 naive. The ORR was 71.9%, including 15.2% complete and 56.7% partial responses. Median DOR in the overall cohort was 20.96 months (95% CI, 15.71-26.22). In the IPTW-weighted analysis, prior T-DM1 exposure was associated with significantly shorter PFS: 12.1 months (95% CI, 10.3-20.5) versus 26.0 months (95% CI, 18.9 - not reached) in T-DM1 naive patients (IPTW-weighted log-rank p = 0.006). Prior T-DM1 remained independently associated with higher progression risk (HR 1.99, 95% CI 1.09 - 3.62; p = 0.02). Median OS was 18.9 months (95% CI, 17.2-not reached) in T-DM1 pretreated patients and not reached in T-DM1 naive patients; the IPTW-weighted OS hazard ratio did not reach statistical significance (HR 1.80, 95% CI 0.86-3.79; p = 0.12). CONCLUSIONS: Trastuzumab deruxtecan demonstrated substantial real-world activity after prior T-DM1 exposure, but PFS was significantly shorter compared with T-DM1 naive patients, even after rigorous adjustment for measured confounding. These findings highlight the clinical relevance of antibody drug conjugate sequencing and support prospective studies to define the optimal positioning of T-DXd in HER2 positive mBC treatment algorithms.