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.

Perspectives: Other ErbB2-Targeted Therapies.

Abstract: Summary Despite the success of individualized targeted therapies in women with breast cancer with current available compounds, new drugs – especially with different mechanisms of resistance – are under development. A range of novel targeted agents for women with tumors that overexpress ErbB2 (HER2) and progress on trastuzumab and lapatinib have entered clinical studies. Most of these agents are monoclonal antibodies or multifunctional tyrosine kinase inhibitors. Recently published data even showed encouraging synergistic effects of several new substances, which in the future could pose as a chemotherapy-free treatment option in the metastatic setting.

Neoadjuvant chemotherapy (NACT) and HER2 double inhibition including biosimilar trastuzumab (ONTRUZANT) for HER2-positive early breast cancer (EBC): Population-based real world data from the Danish Breast Cancer Group (DBCG).

Abstract: 577Background: Increasingly, HER2-positive early breast cancer (EBC) is treated by NACT combined with trastuzumab and pertuzumab followed by surgery. Ontruzant is registered as a biosimilar trastuz...

Abstract OT1-02-09: A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC) (HER2CLIMB)

Abstract: Background: ONT-380 is a highly selective small molecule inhibitor of HER2 kinase with nanomolar potency. Unlike dual HER2/EGFR agents, it does not inhibit EGFR at clinically relevant concentrations, decreasing the potential for EGFR-related toxicities (severe skin rash and diarrhea). In preclinical studies, ONT-380 demonstrated synergistic activity with T, and was active in HER2+ models of brain metastases (mets). In a Phase 1b study, ONT-380 was combined with C and T in pts with HER2+ MBC previously treated with trastuzumab emtansine (T-DM1) and T. Objective responses were seen, including in pts with brain mets. The combination was well tolerated, with low rates of Gr 3 diarrhea at the recommended dose (300 mg PO BID, equivalent to the single agent MTD). Based on these data, ONT-380 is now being evaluated in a Phase 2 study in combination with C and T (HER2CLIMB). Trial Design: The primary study objective is to assess the effect of ONT-380 vs. placebo given with C + T on progression-free survival (PFS) based on independent central review. Additional objectives include ORR, duration of response, clinical benefit rate, and safety. The study population includes adult pts with progressive HER2+ locally advanced or MBC who have had prior treatment with a taxane, T, pertuzumab and T-DM1 but not C or lapatinib. Pts with brain mets,including untreated or progressive mets, may be enrolled. 180 pts will be enrolled in North America and Europe. Pts are receiving C (1000 mg/mg2 PO BID for 14 days of a 21-day cycle) and T (8 mg/kg IV loading dose; 6 mg/kg IV once every 21 days), and are being randomized in a 2:1 ratio to ONT-380 300 mg PO BID or placebo. Pts with isolated CNS progression may continue on study treatment after undergoing local CNS therapy. An independent Data Monitoring Committee is monitoring pt safety. Citation Format: Hamilton E, Borges V, Murthy R, Anders C, Cameron D, Carey L, Muller V, Curigliano G, Gelmon K, Hortobagy G, Krop I, Loibl S, Pivort X, Pegram M, Slamon D, Hurvitz S, Tsai M, Winer E. A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC) (HER2CLIMB) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-02-09.

Axillary Downstaging and the Impact of Clinical Axillary Status on Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer: A Network Meta-Analysis

Abstract: Background: Lymph node downstaging and the achievement of total-pCR (ypT0/is ypN0) after neoadjuvant therapy are of great importance in HER-2 positive breast cancer. We aim to provide an overall review of neoadjuvant regimens for lymph node downstaging and to indirectly compare the total-pCR by various neoadjuvant regimens with network meta-analysis in HER2-positive patients according to their clinical lymph node status. Methods: Five English databases were searched comprehensively and systematically for relevant RCTs and case-control studies. The data extracted from the included studies were analyzed with the use of Review Manager 5.3 or STATA 15.0 software. Results: A total of 1508 published manuscripts were identified, and 17 studies including 4747 patients were finally included in our analysis. The network meta-analysis of total-pCR showed that dual-target therapy is significantly better than single-target therapy in clinically node-positive patients, and carboplatin performed significantly better than anthracycline in single-target condition. Lapatinib performed poorly in clinically node-positive patients. However, lapatinib in combination with trastuzumab was ranked at the top in the clinically node-negative group, and pertuzumab showed dissatisfied performance in contrast to the primacy of pertuzumab in clinically node-positive groups. Conclusion: In summary, different lymph node statuses led to the diverse first choice of neoadjuvant regimen. We highly recommended TCbHP as the first choice for the neoadjuvant treatment in clinically node-positive HER-2 positive breast cancer. Since lapatinib with trastuzumab ranked top in the clinically node-negative group, we looked forward to discovering the potential value of TKI in clinically node-negative patients, which needs further analysis in the future.