皮下注射曲妥珠单抗治疗乳腺癌
曲妥珠单抗静脉注射制剂每次用药通常需要30～90分钟，加入重组人源化透明质酸酶的曲妥珠单抗皮下注射制剂可以将每次注射时间缩短至5分钟，III期非盲随机对照研究HannaH已经证实曲妥珠单抗皮下注射与静脉注射相比，对于HER2阳性、可手术、局部晚期或炎性乳腺癌患者的安全性和有效性相似，临床相关不良事件较少，尤其治疗相关不良事件，例如给药部位反应。曲妥珠单抗皮下注射制剂包括两种装置：手持式注射器（安瓿）和单次注射装置。
2018年11月2日，欧洲癌症治疗研究组织、欧洲癌症组织、欧洲乳腺癌专科学会《欧洲癌症杂志》在线发表意大利罗氏、米兰圣拉斐尔科学研究所、坎迪奥洛癌症研究所、威尼斯安基罗医院、圣厄休拉·马尔比基医院、博洛尼亚医院、雷焦艾米利亚新玛丽亚医院、拉马齐尼医院、格罗塞托慈善医院、圣心唐卡拉布里亚医院的研究报告，评定了曲妥珠单抗皮下注射制剂对HER2阳性早期或局部晚期乳腺癌的安全性和耐受性。
SCHEARLY: A Study of the Safety of Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Early and Locally Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (NCT01940497)
该前瞻非盲非随机意大利多中心双组研究SCHEARLY隶属于UmbHER1研究，于2013年12月～2014年10月从52个意大利研究中心入组HER2阳性早期或局部晚期乳腺癌患者240例（术后辅助治疗占81.7%，术前新辅助治疗占18.3%），皮下注射曲妥珠单抗600mg治疗1年。按入组时间先后将患者分入手持式注射器组121例和单次注射装置组119例。术后辅助或术前新辅助治疗包括蒽环类化疗8个周期→皮下注射曲妥珠单抗＋紫杉类化疗4个周期→皮下注射曲妥珠单抗14个周期，随访2年。
结果，完成治疗201例，早期停药占7.5%，主要由于并发不良事件。完成不良事件随访228例，总体而言，两组安全性相似，治疗相关不良事件发生率：
≥3级不良事件：3.9%
严重不良事件：0.9%（胸膜心包炎1例、过敏性休克1例，均已解决）
心脏不良事件：14.5%（与既往研究结果相似）
左心室射血分数减少：7.9%（从筛查至随访平均减少2.9%）
充血性心力衰竭：无
全身给药相关反应：68.0%（1～2级为主）
局部注射部位反应：21.9%（1～2级为主）
因此，根据该研究结果，皮下注射曲妥珠单抗600mg被证实为HER2阳性早期或局部晚期乳腺癌患者安全且可耐受的辅助或新辅助治疗方案。大多数患者和医疗专业人员倾向皮下注射曲妥珠单抗而非静脉注射曲妥珠单抗。
Eur J Cancer. 2018 Nov 2;105:61-70.
Safety profile of subcutaneous trastuzumab for the treatment of patients with HER2-positive early or locally advanced breast cancer: primary analysis of the SCHEARLY study.
Milvia Zambetti, Filippo Montemurro, Paolo Morandi, Claudio Zamagni, Alba A. Brandes, Giancarlo Bisagni, Katia Cagossi, Carmelo Bengala, Stefania Gori, Claudio Iannacone, Alessia Stell, Luca Gianni.
San Raffaele Scientific Institute, Milan, Italy; Candiolo Cancer Institute, Candiolo, Italy; Ospedale Dell'Angelo, Mestre-Venezia, Italy; Policlinico Sant'Orsola Malpighi, Bologna, Italy; AUSL Bologna-ISNB, Bologna, Italy; IRCCS Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy; B. Ramazzini Hospital, Carpi, Italy; Misericordia Hospital, Grosseto, Italy; IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy; SPARC Consulting Srl, Milan, Italy; Roche S.p.A., Monza, Italy.
HIGHLIGHTS
Subcutaneous trastuzumab (H SC) confirms to be a safe and tolerable option in patients with HER2-positive early and locally advanced breast cancer.
Administration-related adverse events were mostly of grade I-II.
Cardiotoxicity was consistent with previous findings.
Most patients and healthcare professionals would prefer H SC over intravenous trastuzumab.
BACKGROUND: Subcutaneous trastuzumab (H SC) is a valuable alternative to the intravenous formulation. This study assessed H SC safety and tolerability in human epidermal growth factor receptor 2 (HER2)+ early/locally advanced breast cancer (EBC/LABC).
METHODS: SCHEARLY is a prospective, two-cohort, non-randomised, multicentre Italian trial included in the umbrella study UmbHER1, planning a 1-year treatment with H SC 600 mg in HER2+ EBC/LABC. Patients were sequentially assigned to cohort A (N = 121) and B (N = 119) to receive H SC via a handheld syringe and a single-use injection device, respectively. Adjuvant or neoadjuvant treatment included anthracycline-containing regimens followed by H SC plus taxanes and then alone for 18 cycles totally.
RESULTS: Two hundred forty patients were enrolled (adjuvant therapy: 81.7%; neoadjuvant therapy: 18.3%), and 201 completed the treatment (early discontinuation was mainly due to intercurrent adverse events [AEs], 7.5%). Overall, the two cohorts displayed similar safety profiles. From H SC start, the rate of treatment-related AEs in the safety population (N = 228) was 3.9% for grade ≥3 AEs; 0.9% for serious AEs (one pleuropericarditis and one anaphylactic shock, both resolved) and 14.5% for cardiac AEs, the most common being the decreased left ventricular ejection fraction (7.9%; mean reduction from the screening to the follow-up visit was 2.9%). No cases of congestive heart failure occurred. The rate of systemic administration-related reactions and local injection site reactions was 68.0% and 21.9%, respectively, mostly of grade 1-2.
CONCLUSIONS: H SC 600 mg confirmed to be a safe and tolerable option as adjuvant/neoadjuvant therapy in patients with HER2+ EBC and LABC.
ClinicalTrials.gov Identifier: NCT01940497
KEYWORDS: Early/locally advanced breast cancer, Cardiotoxicity, HER2, Safety, Subcutaneous trastuzumab
DOI: 10.1016/j.ejca.2018.09.034
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