Krasniqi Eriseld, Filomeno Lorena, Arcuri Teresa, Di Lisa Francesca Sofia, Astone Antonio, Cutigni Claudia, Foglietta Jennifer, Nunzi Martina, Rossi Rosalinda, Minelli Mauro, Meattini Icro, Visani Luca, Scialino Jacopo, Livi Lorenzo, Moscetti Luca, Marchetti Paolo, Botticelli Andrea, Paris Ida, Pavese Francesco, D'Angelo Tatiana, Sini Valentina, Stani Simonetta, Valerio Maria Rosaria, Grassadonia Antonino, Tinari Nicola, Mazzotta Marco, Vergati Matteo, D'Auria Giuliana, Gamucci Teresa, D'Onofrio Loretta, Gasparro Simona, Roselli Arianna, Fulvi Alberto, Ferretti Gianluigi, Torchia Andrea, Giordano Monica, Greco Filippo, Pantano Francesco, Tonini Giuseppe, Fabbri Agnese, Bria Emilio, Garufi Giovanna, Fiorio Elena, Raffaele Mimma, Pistelli Mirco, Berardi Rossana, Saltarelli Rosa, Kayal Ramy, Ferranti Francesca Romana, Cannita Katia, Irelli Azzurra, D'Ostilio Nicola, De Rossi Costanza, Palumbo Raffaella, Cariello Anna, Sanguineti Giuseppe, Calabrò Fabio, Pizzuti Laura, Barba Maddalena, Botti Claudio, Pelle Fabio, Cappelli Sonia, Cavicchi Flavia, Puccica Ilaria, Villanucci Amedeo, Sperduti Isabella, Ciliberto Gennaro, Vici Patrizia
Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
Medical Oncology Unit, San Giovanni Evangelista Hospital, ASL RM5, 00019 Tivoli, Italy.
Cancers (Basel). 2024 Dec 7;16(23):4104. doi: 10.3390/cancers16234104.
BACKGROUND/OBJECTIVES: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting. The secondary objective was to assess the effectiveness.
This was a multicenter, retrospective study across 24 Italian oncology centers, including 410 patients with HER2BC treated with adjuvant T-DM1 following a lack of pCR after NAT. Patient characteristics, NAT regimens, and surgical outcomes were recorded. Tolerability was assessed by documenting adverse events (AEs) according to the CTCAE (v5.0). Preliminary effectiveness was evaluated in terms of relapse-free survival (RFS) and overall survival (OS).
Overall, 228 patients (55.6%) experienced at least one AE related to T-DM1, with 4.9% experiencing grade 3 or higher AEs. The most common AEs were hepatotoxicity (18.5%) and thrombocytopenia (17.6%). T-DM1 was discontinued in 10.0% of patients due to toxicity. After a median follow-up of 25 months, 31 relapse events (7.6%) and 22 deaths (5.4%) were reported. The preliminary incidence of RFS and OS events was similar between patients who completed the T-DM1 course and those who discontinued it early.
T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required.
背景/目的：人表皮生长因子受体2阳性乳腺癌（HER2阳性乳腺癌）是一种侵袭性亚型，新辅助治疗（NAT）旨在实现病理完全缓解（pCR）以改善长期预后。对于未获得pCR的HER2阳性乳腺癌患者，曲妥珠单抗 emtansine（T-DM1）已被确立为辅助治疗的标准方案。ATD研究旨在评估T-DM1在此情况下的真实世界耐受性。次要目的是评估其有效性。
这是一项在意大利24个肿瘤中心开展的多中心回顾性研究，纳入了410例HER2阳性乳腺癌患者，这些患者在新辅助治疗后未达到pCR，随后接受辅助性T-DM1治疗。记录患者特征、新辅助治疗方案和手术结果。根据美国国立癌症研究所不良事件通用术语标准（CTCAE，第5.0版）记录不良事件（AE）来评估耐受性。从无复发生存期（RFS）和总生存期（OS）方面评估初步有效性。
总体而言，228例患者（55.6%）经历了至少1次与T-DM1相关的不良事件，4.9%的患者经历了3级或更高级别的不良事件。最常见的不良事件是肝毒性（18.5%）和血小板减少症（17.6%）。10.0%的患者因毒性反应停用T-DM1。中位随访25个月后，报告了31例复发事件（7.6%）和22例死亡（5.4%）。完成T-DM1疗程的患者与提前停药的患者之间，无复发生存期和总生存期事件的初步发生率相似。
T-DM1显示出可控的安全性，不良事件与随机试验中报告的一致。现有数据尚不足以对无复发生存期和总生存期进行正式分析，需要长期随访。
