赫赛汀新剂型（subcutaneous Herceptin，Herceptin SC）
曲妥珠单抗+透明质酸
商品名：赫赛汀SC
条目类型：新剂型
英国：批准（许可）
欧盟：批准（许可）
美国：第三期临床试验
英国推出计划：仅注册用户
英国实际推出日期：
04/09/2013获欧盟批准。
罗氏Herceptin SC皮下注射剂型赫赛汀获欧盟批准
2013年9月3日，罗氏（Roche）宣布，皮下注射剂型赫赛汀（subcutaneous Herceptin，Herceptin SC）获欧盟委员会（EC）批准，用于HER2阳性乳腺癌的治疗。
目前，Herceptin通过静脉滴注（intravenous，IV）给药，全程耗时30-90分钟，皮下注射剂型Herceptin则通过皮下注射（subcutaneous，SC）给药，耗时仅为2-5分钟，创伤更小，耗时更短，为HER2阳性乳腺癌患者提供了一个重要的治疗选择。
皮下注射剂型Herceptin的获批，是基于关键性III期HannaH研究的结果。数据表明，皮下注射剂型Herceptin具有与静脉注射剂型Herceptin相一致的疗效和安全性。
Herceptin SC是一种固定剂量（600mg/5ml）的即用型（ready-to-use）液体配方，每3周给药一次，不再需要根据患者的体重计算给药的剂量，从而简化了护理程序。
赫赛汀新剂型Herceptin SC， 利用Halozyme公司新一代透明质酸酶技术开发，能够瞬时及可逆地降解皮下细胞之间的透明质酸屏障，从而使5ml体积的皮下注射剂型Herceptin在更大面积的皮下组织中迅速分散和吸收。
说明书附件：https://www.medicines.org.uk/emc/medicine/28179
Herceptin SC
Herceptin SC reduces treatment times and enhances convenience compared to the standard intravenous (IV) form.
"With pricing on par with the intravenous formulation, Herceptin SC represents a compelling treatment alternative for breast cancer patients in Europe, and we congratulate Roche on making this time-saving therapy available to patients in Europe so quickly," said Gregory I. Frost, Ph.D., President and Chief Executive Officer of Halozyme. "This will be the third commercial product using our rHuPH20 enzyme and represents a significant achievement for our technology and company as a whole."
About Breast Cancer Breast cancer is the most common cancer among women worldwide.1 Each year, about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 women will die of the disease annually.1 In HER2-positive breast cancer, increased quantities of the human epidermal growth factor receptor 2 (HER2) are present on the surface of the tumor cells. This is known as "HER2 positivity" and affects approximately 15% to 20% of women with breast cancer.2 HER2-positive cancer is a particularly aggressive form of breast cancer.
Information
Generic Name: trastuzumab + hyaluronidase
Trade Name: Herceptin SC
Entry Type: New formulation
Developmental Status
UK: Approved (Licensed)
EU: Approved (Licensed)
US: Phase III Clinical Trials
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Sep 13: Approved in the EU [14].
04/09/2013 10:12:23
Jul 13: Recommended approval in the EU for the treatment of patients with HER2-positive breast cancer [11].
01/07/2013 09:10:22
Mar 12: Filed in EU [5].
09/03/2012 22:00:54
EU filing planned 2012 [2].
07/09/2011 17:04:03
Trial or other data
Aug 13: NCT01926886 is a single arm multi-centre PIII study investigating the at home administration, by a health care professional, of s.c. trastuzumab for the treatment of 100 patientswith HER2-positive early breast cancer. The primary outcome is safety. The study starts Sep 13 and is due to complete May 17 [13].
22/08/2013 11:51:28
Aug 13: Randomised PrefHer study (NCT01401166) assessing patient preference for either SC or IV trastuzumab published in Lancet Oncology. 236 women aged 18 years or older with HER2-positive, histologically confirmed primary invasive breast adenocarcinoma, no evidence of residual, locally recurrent, or metastatic disease after completion of surgery and chemotherapy (neoadjuvant or adjuvant), an ECOG performance status of 0 or 1, and a baseline left-ventricular ejection fraction of 55% or more before the first dose of trastuzumab received four cycles of 600 mg fixed-dose SC adjuvant trastuzumab via a single-use injection device or hand-held syringe followed by four cycles of standard IV trastuzumab, or the reverse sequence. SC trastuzumab via the single-use injection device was preferred by 216 patients (91·5% [95% CI 87·2—94·7]; p<0·0001). Only 16 patients preferred IV trastuzumab (6·8% [3·9—10·8]), & four had no preference (1·7% [0·5—4·3]). Clinician-reported adverse events occurred in 141 of 242 (58%) pts during the pooled SC periods & 105 of 241 (44%) pts during the pooled IV periods; seven (3%) & five (2%) were grade 3, no pts had a grade 4 or 5 event. The most common grade 3 adverse event was influenza (0·8%) [12].
22/08/2013 10:30:03
Aug 12: HannaH published early online in Lancet Oncology [10].
10/08/2012 10:07:07
Hyaluronidase facilitates penetration & dispersion of trastuzumab by temporarily digesting hyaluronan, a major component of extracellular matrix in tissues such as skin [9].
01/05/2012 09:15:35
Apr 12: NCT01566721 a PIII prospective, two-cohort non-randomized, multi-centre, multinational, open label study to assess the safety of assisted- and self-administered subcutaneous trastuzumab as adjuvant therapy in 2,500 patients with operable HER2-positive early breast cancer [SafeHer Study]. The study started Mar 12 [7]
02/04/2012 14:42:33
Mar 12: Results from the PIII HannaH study in women with HER2-positive eBC reported. The co-primary endpoints of pharmacokinetics and efficacy met their pre-specified criteria. Plasma concentration measured just before surgery was at least as high for the SC as for the IV formulation (69.0 and 51.8 µg/mL, respectively). In addition, efficacy as determined by pathological complete response (pCR; complete eradication of the tumour cells in the breast), was in the same range as in patients who received the and SC IV formulations(45.4% and 40.7%, respectively). The overall safety profile was consistent with that expected from treatment with Herceptin and standard chemotherapy in this setting. The results were presented at the 8th European Breast Cancer Conference (EBCC-8) in Vienna (Abstract # 1BA) [6].
02/04/2012 10:25:29
Q4 11: Positive top-line data from HANNAH (NCT00950300) trial, reported in Oct, has been accepted for presentation at EBCC 2012 [4].
06/03/2012 15:28:10
Oct 11: Positive results from the PIII showed SC injection of trastuzumab had comparable results to the IV infusion. The SC administration takes around 5 minutes to administer whereas the IV formulation (the current standard) takes around 30 minutes to infuse. Since the subcutaneous administration is an injection under the skin it may allow patients to spend less time in hospital receiving their treatment versus the intravenous method. The ready to use formulation may also significantly reduce pharmacy time as no medicine preparation time is required [3].
19/10/2011 09:35:05
NCT00950300: a PIII randomized open-label study comparing the pharmacokinetics, efficacy and safety of subcutaneous vs IV trastuzumab in 593 women with HER2-positive early breast cancer. Patients with operable or locally advanced breast cancer will receive pre-operative treatment with 8 cycles of chemotherapy (docetaxel followed by 5-FU/ epirubicin/ cyclophosphamide) concurrent with either SC or IV trastuzumab. After surgery patients will receive a further 10 cycles of trastuzumab SC or IV to complete 1 year of treatment. Patients will be followed for up to 2 years after the end of treatment. The primary outcome measures are: trastuzumab serum concentrations, throughout cycles 1 to 8; pathologic complete response after surgery between cycles 8 and 9. The study started in Sep 09 and is due to complete Jun 14 [1].
22/08/2011 09:00:12
Evidence Based eva luations
References
Available only to registered users
Category
BNF Category: Other antineoplastic drugs (08.01.05)
Pharmacology: HER2 monoclonal antibody co-formulated with recombinant human hyaluronidase
Epidemiology: Breast cancer is the most common cancer in women, with about 45,000 new cases in the UK each year. In Britain the age-standardised incidence of breast cancer per 100,000 women was 122 in 2006 [8].
Indication: Breast cancer
Additional Details: early & metastatic HER2+ve disease, subcutaneous formulation
Method(s) of Administration
Subcutaneous
Company Information
Name: Roche
US Name: Roche
NICE Information
In timetable: No
When:
PBR Chemotherapy is tariff excluded.
Service
Implications Available only to registered users
Prescribing
Outlook: Available only to registered