Department of Obstetrics and Gynecology and Breast Cancer and Gynecology Cancer Center, Sana Klinikum Offenbach GmbH, Offenbach, Germany
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Ann Oncol. 2015 Feb;26(2):320-5. doi: 10.1093/annonc/mdu524. Epub 2014 Nov 17.
HannaH (NCT00950300) was a phase III, randomized, international, open-label study that compared pharmacokinetics (PK), efficacy, and safety of two different trastuzumab formulations [subcutaneous (s.c.) and intravenous (i.v.)] in HER2-positive, operable, locally advanced, or inflammatory breast cancer in the neoadjuvant/adjuvant setting. The co-primary end points, to show noninferiority of s.c. versus i.v. trastuzumab in terms of serum concentration (Ctrough) and pathologic complete response (pCR) were met; safety profiles were comparable at 12 months' median follow-up. Secondary end points included safety and tolerability, PK profile, immunogenicity, and event-free survival (EFS). We now report updated safety and efficacy data after a median follow-up of 20 months.
Patients (N = 596) were treated with eight cycles of neoadjuvant chemotherapy, administered concurrently with 3-weekly s.c. trastuzumab (fixed dose of 600 mg) or the standard weight-based i.v. method. Following surgery, patients continued trastuzumab treatment to complete 1 year of therapy. Updated analyses of PK, efficacy, safety, and immunogenicity data were carried out.
s.c. trastuzumab was generally well tolerated and the incidence of adverse events (AEs), including grade 3 or 4 AEs, between treatment groups was comparable. A slightly higher incidence of serious AEs (SAEs), mainly due to infections, was reported with s.c. treatment {64 [21.5%; 95% confidence interval (CI) 17.0%-26.7%] versus 42 (14.1%; 95% CI 10.4%-18.6%) in the i.v. group}; however, the differences were small and often based on rare events, with no observable pattern across reported events. An early analysis of EFS showed rates of 95% in both groups 1 year postrandomization. Exploratory analyses did not reveal an association between toxicity and body weight or exposure.
Overall, the safety profile of s.c. trastuzumab was consistent with the previously published data from HannaH and the known safety profile of i.v. trastuzumab. EFS rates were comparable between the i.v. and s.c. groups.
NCT00950300.
HannaH（NCT00950300）是一项 III 期、随机、国际、开放性研究，比较了曲妥珠单抗两种不同制剂（皮下[SC]和静脉[IV]）在新辅助/辅助治疗 HER2 阳性、可手术、局部晚期或炎性乳腺癌中的药代动力学（PK）、疗效和安全性。主要终点是证明 SC 与 IV 曲妥珠单抗在血清浓度（Ctrough）和病理完全缓解（pCR）方面具有非劣效性；在 12 个月的中位随访中，安全性谱相当。次要终点包括安全性和耐受性、PK 谱、免疫原性和无事件生存（EFS）。我们现在报告中位随访 20 个月后的更新安全性和疗效数据。
患者（N=596）接受了 8 个周期的新辅助化疗，同时给予 3 周一次的 SC 曲妥珠单抗（固定剂量 600mg）或标准基于体重的 IV 方法。手术后，患者继续接受曲妥珠单抗治疗，完成 1 年的治疗。对 PK、疗效、安全性和免疫原性数据进行了更新分析。
SC 曲妥珠单抗总体耐受性良好，治疗组之间不良事件（AE）的发生率，包括 3 级或 4 级 AE，相当。报告的 SC 治疗组严重不良事件（SAE）发生率略高，主要是感染所致{64 [21.5%；95%置信区间（CI）17.0%-26.7%]与 IV 组 42 例（14.1%；95% CI 10.4%-18.6%）}；然而，差异很小，且通常基于罕见事件，报告的事件之间没有明显的模式。EFS 的早期分析显示，随机分组后 1 年两组的 EFS 率均为 95%。探索性分析未发现毒性与体重或暴露之间存在关联。
总体而言，SC 曲妥珠单抗的安全性与之前 HannaH 发表的数据和 IV 曲妥珠单抗的已知安全性一致。IV 组和 SC 组的 EFS 率相当。
NCT00950300。
