Introduction: Approval of the HER2-targeted antibody trastuzumab dramatically improved outcomes for patients with HER2-positive breast cancer. Multiple trastuzumab biosimilars, including ABP 980, are in clinical development. Biosimilars are not identical to the reference biologic, but exhibit equivalence and safety in analytical and clinical studies.
Areas covered: A brief introduction to trastuzumab, overview of trastuzumab biosimilars, and detailed review of ABP 980 preclinical and clinical studies are included. We searched PubMed and 2016–2017 ASCO and ESMO conference proceedings for ‘ABP 980’ or ‘trastuzumab biosimilar’. ‘ABP 980 and breast cancer’ or ‘trastuzumab biosimilar and breast cancer’ were used to search clinicaltrials.gov for phase III trials. Analytical studies of ABP 980 pharmacokinetics (PK) or pharmacodynamics (PD), phase I studies of ABP 980 safety and PK/PD, and phase III studies of clinical efficacy vs trastuzumab are included.
Expert opinion: Questions remain regarding long-term impact of biosimilars on overall healthcare costs, insurance coverage of multiple approved biosimilars, and extensive clinical safety and efficacy follow-up. By producing a competitive market, trastuzumab biosimilars are anticipated to improve access to standard of care therapies, although real-world evidence remains to be obtained. Increased global access to HER2-targeted therapy may eventually alter the landscape of breast cancer and survival rates. 相似文献
Introduction: Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate (ADC) that combines intracellular delivery of the potent cytotoxic agent, DM1 (a derivative of maytansine) with the antitumor activity of trastuzumab. While there are several ADCs in Phase III development, T-DM1 is the only one in which the targeting antibody has antitumor properties. T-DM1 is also the only ADC that is directed toward the human EGFR 2 (HER2). Effective therapies are limited in HER2-positive advanced or metastatic breast cancer (MBC), particularly following progression on available HER2-targeted therapies. Areas covered: The mechanisms of action, preclinical efficacy and clinical profile of T-DM1 are reported. The latest preclinical and clinical data for T-DM1 are examined. Expert opinion: T-DM1 has significant antitumor potency in vitro and in vivo, which is maintained in tumors resistant to trastuzumab or lapatinib. In Phase I and II trials, T-DM1 provided objective tumor responses and was well tolerated across various lines of therapy in patients with HER2-positive MBC. In addition, it showed similar efficacy to trastuzumab plus docetaxel in first-line MBC. Ongoing trials (including two Phase III studies) are investigating T-DM1 as single-agent therapy or combined with other chemotherapeutic or biologic agents, and the results should help to define the place of T-DM1 within current treatment algorithms for HER2-positive disease. 相似文献
ABSTRACTIntroduction: CT-P6 (trastuzumab-pkrb, Herzuma) is a trastuzumab biosimilar approved for use in HER2 positive breast cancer and HER2 positive gastric cancer. CT-P6 has been shown to exhibit similar safety and efficacy profiles to its reference product, trastuzumab. Preclinical and clinical studies have been performed to prove equivalence between CT-P6 and the trastuzumab originator.Areas Covered: In this review, we examine the evidence comparing CT-P6 with its reference product, trastuzumab. Both monoclonal antibodies function to target cells that overexpress HER2 on the cell surface. Preclinical pharmacologic modeling of CT-P6 shows a similar mechanism of action to trastuzumab, similar pharmacologic properties and a phase I trial in healthy volunteers showed similar pharmacokinetics. A multicenter phase III randomized clinical trial in patients with early breast cancer showed equivalent safety and efficacy between CT-P6 and trastuzumab. One-year follow-up of patients showed identical rates of cardiotoxicity.Expert Opinion: Preclinical and clinical studies showed CT-P6 pharmacologic profile, safety and efficacy are equivalent to trastuzumab. As such, it is a safe and effective alternative for use in patients with HER2 positive breast cancer and gastric cancer. Its implementation into clinical practice can potentially increase patient access and help financially alleviate overburdened health-care systems. 相似文献
Importance of the field: Differential levels of HER2 expression in normal versus HER2-overexpressing breast carcinomas, together with the demonstration of a key role for HER2 in tumor progression, make HER2 an ideal target for specific therapeutic approaches.Areas covered in this review: This review considers the clinical value of trastuzumab and lapatinib, the two HER2-targeted therapies approved for clinical practice. References were chosen by searching the PubMed and MEDLINE datasets using as search term: ‘HER2’, in association with ‘prognosis’, ‘response’, ‘trastuzumab’, ‘lapatinib’ and ‘resistance’.What the reader will gain: This review deals with HER2 as a target for breast carcinoma treatment, focusing on anti-HER2 therapies used in clinical practice, their merits and shortcomings.Take home message: The benefit of anti-HER2 therapies demonstrated in clinical trials indicates that HER2 is, to date, one of the most promising molecules for targeted therapy. Nevertheless, since tumor cells utilizing alternative growth signaling pathways through transmembrane receptors as well as intracellular signaling transduction molecules can bypass HER2 blockade, a future ambitious aim is the successful combination of anti-HER2 strategies with drugs directed to molecules that contribute to anti-HER2 resistance. 相似文献