Altıntaş Yunus Emre, Kınıkoğlu Oğuzcan, Yıldız Anıl, Işık Deniz, Özkerim Uğur, Öksüz Sıla, Tüylü Tuğba Başoğlu, Sürmeli Heves, Turan Nedim, Odabaş Hatice
Department of Medical Oncology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul 34865, Türkiye.
Department of Medical Oncology, Istanbul University Oncology Institute, Istanbul 34093, Türkiye.
Medicina (Kaunas). 2024 Dec 16;60(12):2069. doi: 10.3390/medicina60122069.
: Metastatic breast cancer (MBC), particularly the HER2-positive subtype, represents a significant clinical challenge, with approximately 20-25% of breast cancer cases demonstrating HER2 overexpression. Trastuzumab, a monoclonal antibody targeting HER2, has significantly improved outcomes in these patients. However, progression after second-line treatments such as trastuzumab emtansine (T-DM1) necessitates exploring subsequent therapeutic options. This study aims to compare the efficacy of trastuzumab plus gemcitabine (GT) with lapatinib plus capecitabine (LC) as third-line treatments in HER2-positive MBC post-T-DM1 failure. : This retrospective study included 98 HER2-positive MBC patients treated between 2017 and 2023 who progressed after T-DM1. Patients were divided into two groups: 21 received GT, and 28 received LC. Key endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events. Statistical analyses were performed using SPSS 26.0, with Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazards models. : Median PFS was significantly longer in the GT group (9.5 months) compared to the LC group (4.3 months, = 0.02). OS was also higher for GT (22.1 months vs. 10.0 months, = 0.02). ORR favored the GT group (33.3% vs. 10.7%, = 0.046), and progressive disease was more common in the LC group (57.1% vs. 33.3%, = 0.022). The safety profile showed higher rates of diarrhea in the LC group, but both regimens were generally well tolerated. : Trastuzumab re-challenge with gemcitabine demonstrated superior PFS, OS, and ORR compared to lapatinib plus capecitabine, suggesting it may be a more effective third-line therapy in HER2-positive MBC patients who have progressed after T-DM1. Further prospective studies are needed to confirm these findings and optimize treatment sequencing.
转移性乳腺癌（MBC），尤其是HER2阳性亚型，是一项重大的临床挑战，约20%-25%的乳腺癌病例表现出HER2过表达。曲妥珠单抗是一种靶向HER2的单克隆抗体，显著改善了这些患者的治疗效果。然而，在二线治疗如曲妥珠单抗 emtansine（T-DM1）后出现疾病进展，就需要探索后续的治疗选择。本研究旨在比较曲妥珠单抗联合吉西他滨（GT）与拉帕替尼联合卡培他滨（LC）作为HER2阳性MBC患者T-DM1治疗失败后的三线治疗的疗效。 本回顾性研究纳入了98例在2017年至2023年间接受治疗且T-DM1治疗后疾病进展的HER2阳性MBC患者。患者分为两组：21例接受GT治疗，28例接受LC治疗。主要终点包括无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和不良事件。使用SPSS 26.0进行统计分析，采用Kaplan-Meier生存曲线、对数秩检验和Cox比例风险模型。 与LC组（4.3个月，P = 0.02）相比，GT组的中位PFS显著更长（9.5个月）。GT组的OS也更高（22.1个月对10.0个月，P = 0.02）。ORR更倾向于GT组（33.3%对10.7%，P = 0.046），疾病进展在LC组更为常见（57.1%对33.3%，P = 0.022）。安全性方面，LC组腹泻发生率更高，但两种治疗方案总体耐受性良好。 与拉帕替尼联合卡培他滨相比，曲妥珠单抗联合吉西他滨再次治疗显示出更好的PFS、OS和ORR，表明它可能是T-DM1治疗后疾病进展的HER2阳性MBC患者更有效的三线治疗方法。需要进一步的前瞻性研究来证实这些发现并优化治疗顺序。
