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.

Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting.

Abstract: Despite relevant medical advancements, metastatic breast cancer remains an uncurable disease. HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer. Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as preferred second line choice. However, there is no prospectively designed available study focusing on the sequence and outcomes of patients treated with T-DM1 following the triplet. In the following report, data concerning a wide series of patients treated in a real-life setting are presented. Results obtained in terms of response and median progression free survival suggests a significant role for T-DM1 in disease control of metastatic HER2 expressing breast cancer.

Abstract P3-14-22: Pharmacokinetics (PK) of Trastuzumab-DM1 (T-DM1) and Paclitaxel (T) in Patients with HER2-Positive Locally Advanced or Metastatic Breast Cancer (MBC) Previously Treated with a Trastuzumab-Containing Regimen

Abstract: Background T-DM1 is an antibody-drug conjugate composed of DM1 conjugated to trastuzumab. T-DM1 combines the antitumor properties of trastuzumab with the antimicrotubule activity of DM1. Nonclinical data suggest synergy for the combination of T-DM1 and taxanes. T-DM1 is expected to undergo proteolytic degradation with no significant involvement of cytochrome P450 isoenzymes (CYPs). DM1 is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5. T is metabolized primarily by CYP2C8 and to minor metabolites by CYP3A4. Neither DM1 nor T inhibit or induce CYPs at clinically relevant concentrations. Since T and DM1 are substrates of CYPs, their PK may be altered by interaction with other compounds that are substrates, inhibitors or inducers of CYPs. Given these metabolic pathways, it is important to evaluate if a PK-based drug-drug interaction potential exists when T-DM1 and T are administered together. Methods The tolerability, PK and dose-limiting toxicities of T-DM1 (q3w and qw) and T (qw) (and pertuzumab in subsequent cohorts) in patients with HER2- positive MBC previously treated with a trastuzumab-containing regimen were investigated in this 3+3 phase Ib study, TDM4652g. In Part 1, patients received T-DM1 (2.4 mg/kg or 2.0 mg/kg q3w) and T (65 mg/m2 or 80 mg/m2 qw). In Cycle 1 of all cohorts there was a planned 1-day delay between T and T-DM1 administration; in later cycles, T was administered immediately after T-DM1, allowing within study PK comparisons of T ± T-DM1. Study patients were evaluated for serum concentrations of T-DM1, total trastuzumab (conjugated and unconjugated to DM1), and plasma concentrations of DM1 and T, at prespecified time points. PK of T-DM1 and related analytes were compared to historical monotherapy data by population analysis and/or noncompartmental analysis (NCA). Whether combination with T was a significant covariate of T-DM1 clearance (CL) and central volume of distribution (V1) was tested. PK parameters of T at Cycle 1 (without T-DM1) and Cycle 2 (with T-DM1) were estimated and compared by NCA. Results from 14 patients enrolled in Part 1 are reported here. Results The maximal concentration (Cmax) and area under the concentration-time curve (AUC) values (days 0-7) of T-DM1 in combination treatment were comparable with historical monotherapy data (Table 1) as was the PK of total trastuzumab and DM1. Maximum DM1 level was .05, by log likelihood ratio test). The PK for T was comparable from Cycle 1 (without T-DM1) and Cycle 2 (with T-DM1) for Cmax, AUC, half-life, CL and steady-state volume of distribution. Conclusions This assessment suggests a low potential for PK-based T-DM1 T interaction when these drugs are given in combination therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-22.

Targeted therapy for advanced solid tumors based on molecular profiles: Early results from MyPathway, an open-label, phase IIa umbrella basket study.

Abstract: LBA11511Background: The MyPathway study (NCT02091141) evaluates agents targeting the HER2, BRAF, Hedgehog (Hh), or EGFR pathways in non-indicated tumors with relevant genetic abnormalities. Early results from MyPathway merit pre-planned tumor-cohort expansion. Methods: Eligible pts had advanced solid tumors with no curative therapy and molecular alterations in HER2, BRAF, Hh, or EGFR. Pts received standard doses of trastuzumab + pertuzumab (for the HER2 pathway), vemurafenib (BRAF), vismodegib (Hh), or erlotinib (EGFR) based on alteration. The primary endpoint is investigator-evaluated response rate within a tumor-pathway cohort (RECIST 1.1). Cohort size and expansion is determined by Simon’s two-stage design criteria. Results: By December 14, 2015, MyPathway included 129 pts with available baseline assessments and alterations in HER2 (n = 82; 53 amplifications, 23 mutations, 5 both, 1 RBMS-NRG1 fusion), BRAF (n = 33; 18 V600E, 15 other), Hh (n = 8; 7 PTCH1, 1 SMO), or EGFR (n = 6). Pts had a median of 3 ...

Update Breast Cancer 2020 Part 3 – Early Breast Cancer

Abstract: The treatment of patients with early breast cancer has always been characterised by escalation by new therapies and de-escalation through identification of better treatment regimens or introduction of better tools to estimate prognosis. Efforts in some of these areas in the last few years have led to solid data. The results of the large studies of de-escalation through use of multi-gene tests are available, as are the results of some studies that investigated the new anti-HER2 substances T-DM1 and pertuzumab in the early treatment situation. Several large-scale studies examining the role of CDK4/6 inhibitors will soon be concluded so innovations can be anticipated in this area also. This review article will summarise and classify the results of the latest publications.