Gupta Anuj, Sansar Bipinesh, Mishra Bal Krishna, Khan Aqusa, Singh Arpita, Upadhyay Arvind, Chowdhury Zachariah, Patne Shashikant, Tripathi Mayank, Shukla Shreya, Singh Satyendra Narayan, Pujari Lincoln, Giridhar Prashanth, Kapoor Ankita Rungta, Suresh Arvind, Dey Somnath, Vinayak Kunal Ranjan, Singh Neha, Kumar Amit, Pal Ankita, Kapoor Akhil
Department of Medical Oncology, Mahamana Pandit Madan Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, India.
Department of Oncopathology, Mahamana Pandit Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Himi Bhabha National Institute, Varanasi, India.
Sci Rep. 2025 May 28;15(1):18669. doi: 10.1038/s41598-025-97923-2.
HER2-positive metastatic breast cancer (MBC) represents a challenging subtype of breast cancer, characterized by aggressive disease and poor clinical outcomes. Trastuzumab emtansine (TDM1), an antibody-drug conjugate combining trastuzumab and emtansine, has demonstrated efficacy in clinical trials as a second-line treatment for patients progressing after prior therapies. This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients. A retrospective analysis was conducted on 70 HER2-positive MBC patients treated with TDM1 at our centre between January 2020 and December 2022. Clinical characteristics, progression-free survival (PFS), overall survival (OS), response rates, and toxicity were evaluated using hospital records. PFS and OS were calculated using Kaplan-Meier methods, and survival curves were compared with log-rank tests. The median age of patients was 47 years, with a majority presenting with advanced disease and prior treatment lines. The median PFS was 6.1 months (95% CI, 4.5-7.6), and the median OS was 14.4 months (95% CI, 10.2-18.0). The objective response rate was 75.7%, with 12.8% achieving a complete response and 62.8% a partial response. PFS was significantly longer in hormone receptor-positive patients compared to hormone receptor-negative patients (8.1 vs. 4.1 months, p = 0.035). Toxicity was manageable, with grade 3-4 adverse events including elevated transaminases (8.5%), thrombocytopenia (5.7%), and anemia (4.2%). The efficacy of TDM1 in this real-world cohort aligns with clinical trial data, though PFS and OS were somewhat lower compared to trials, likely due to the inclusion of patients with more extensive disease and prior treatments. Notably, TDM1 demonstrated activity against CNS metastases and a manageable safety profile, with higher incidence of hepatic and hematologic toxicities. Our study supports the use of TDM1 as a viable option for treating HER2-positive MBC in routine clinical practice, confirming its effectiveness and safety profile observed in clinical trials.
人表皮生长因子受体2（HER2）阳性转移性乳腺癌（MBC）是一种具有挑战性的乳腺癌亚型，其特征为疾病侵袭性强且临床预后较差。曲妥珠单抗 emtansine（TDM1）是一种将曲妥珠单抗与 emtansine 结合的抗体药物偶联物，在临床试验中已证明对先前治疗后进展的患者作为二线治疗具有疗效。本研究旨在提供关于TDM1在HER2阳性MBC患者中的疗效和安全性的真实世界证据。对2020年1月至2022年12月期间在我们中心接受TDM1治疗的70例HER2阳性MBC患者进行了回顾性分析。使用医院记录评估临床特征、无进展生存期（PFS）、总生存期（OS）、缓解率和毒性。使用Kaplan-Meier方法计算PFS和OS，并通过对数秩检验比较生存曲线。患者的中位年龄为47岁，大多数患者表现为晚期疾病并接受过先前的治疗线。中位PFS为6.1个月（95%CI，4.5-7.6），中位OS为14.4个月（95%CI，10.2-18.0）。客观缓解率为75.7%，其中12.8%达到完全缓解，62.8%达到部分缓解。激素受体阳性患者的PFS明显长于激素受体阴性患者（8.1个月对4.1个月，p=0.035）。毒性是可控的，3-4级不良事件包括转氨酶升高（8.5%）、血小板减少（5.7%）和贫血（4.2%）。TDM1在这个真实世界队列中的疗效与临床试验数据一致，尽管与试验相比，PFS和OS略低，这可能是由于纳入了疾病更广泛且接受过先前治疗的患者。值得注意的是，TDM1对中枢神经系统转移显示出活性，且安全性可控，肝毒性和血液学毒性的发生率较高。我们的研究支持在常规临床实践中使用TDM1作为治疗HER2阳性MBC的可行选择，证实了其在临床试验中观察到的有效性和安全性。
