Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.

Abstract P5-20-18: Comparison of paclitaxel plus T-DM1 and pertuzumab versus paclitaxel plus trastuzumab and pertuzumab with carboplatin for HER2 overexpressed breast cancer models

Abstract: Background: Remarkable progressions have been made in the breast cancer treatments over the past years, however, patients getting relief from the toxicity of cancer treatments are still unmet needs. The neoadjuvant regimen of docetaxel, carboplatin, and trastuzumab plus pertuzumab is standard choice for patients with HER2 positive breast cancer (Phase III results of the KRISTINE trial, SA Hurvitz et al., 2016). Trastuzumab emtansine (T-DM1) plus pertuzumab (P) has shown superior anti-tumor effect comparing with trastuzumab/Herceptin (H) plus P in preclinical HER2 positive breast cancer models (Y Sun et al., 2013). In this study we aimed to evaluate the preclinical efficacy of paclitaxel (T) plus T-DM1 and P versus paclitaxel plus H and P with carboplatin (C) (TCHP) in HER2 positive breast cancer models. Methodology: 1) HER2 amplified/overexpressed with ER+ BT474 (H- sensitive) and BT474HerR, an H-resistant derivative from BT474, were used. 2) 6-7 week-old female NCr (nu/nu, 20-25g) athymic mice (Taconic) were used for in vivo tumor growth inhibition studies. 3) Mice were injected s.c. on the flank with 5 x 106 BT474 or BT474HerR cells. All mice were also received s.c. injection of 1 mg/kg estradiol valerate (JHP Pharmaceuticals) once weekly to promote tumor cell growth. 4) Mice bearing BT474 or BT474HerR tumors were treated with different combinations of T (20 mg/kg, i.v., every 4 days, total 7 doses), C (40 mg/kg, i.v., one dose), H (10 mg/kg, i.p., twice weekly for 4 weeks), T-DM1 (10 mg/kg, i.v., every 3 weeks, total 3 doses) and P (15 mg/kg, i.p., once weekly for 8 weeks) versus vehicle control. 5) In vivo data were analyzed by Student9s t-test. A p-value of 0.05 was considered statistically significant. Results: We observed that 1) both regimens of TCHP and paclitaxel plus T-DM1 and P inhibited tumor growth in BT474 (TCHP p Citation Format: Sun Y, Lin X, Jepperson T, Williams C, De P, Leyland-Jones B. Comparison of paclitaxel plus T-DM1 and pertuzumab versus paclitaxel plus trastuzumab and pertuzumab with carboplatin for HER2 overexpressed breast cancer models [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-18.

How to Optimise Extended Adjuvant Treatment with Neratinib for Patients with Early HER2+ Breast Cancer.

Abstract: Over the last 20 years, treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer has considerably improved. The development and addition of (neo)adjuvant trastuzumab to chemotherapy in patients with early HER2+ breast cancer (EHBC) has been shown to provide improvements in both disease-free survival (DFS) and overall survival, with some patients having a good prognosis being candidates for chemotherapy de-escalation strategies. However, despite such promising clinical outcomes, a significant proportion of patients still recur calling for the development of new preventive approaches. To this aim, the use of (neo)adjuvant trastuzumab for longer than one year or followed by lapatinib were tested without additional clinical improvement. Based on more recent advances, therapeutic strategies for patients with HER2+ tumours are now incorporating the use of newer (neo)adjuvant treatments, such as pertuzumab and trastuzumab emtansine, which have shown to further improve the invasive DFS (iDFS) benefit gained with trastuzumab. In this context, the tyrosine kinase inhibitor neratinib is approved in Europe for the extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2+ breast cancer who completed adjuvant trastuzumab-based therapy less than one year ago. Clinical data have demonstrated that neratinib significantly improves iDFS when used for the total recommended duration of 12 months. This review paper provides an overview of the treatment of patients with EHBC, with a focus on the post-trastuzumab use of neratinib.