Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

Laura L Michel,Lothar Häberle,Erik Belleville,Hanna Huebner,Michael Untch,Rachel Wuerstlein,Volkmar Müller,Markus Wallwiener,Jens Huober,Michael P Lux,Bernhard Volz,Diana Lüftner,Wolfgang Janni,Pauline Wimberger,Andreas D Hartkopf,Johannes Ettl,Sara Y Brucker,Friedrich Overkamp,Carsten Hielscher,Peyman Hadji,Hans Tesch,Peter A Fasching,Christoph Mundhenke,Matthias W Beckmann,Andreas Schneeweiß ,Christian M Kurbacher ,D Wallwiener ,Hans‐Christian Kolberg ,Florin‐Andrei Taran ,Tanja Fehm

doi:10.3390/cancers12103021

Abstract

Simple SummaryData about the efficacy of trastuzumab emtansine (T-DM1) following pertuzumab treatment is limited due to the simultaneous development of the two drugs. Thus, the aim of this study was to investigate the efficacy of T-DM1 after previous treatment with pertuzumab in a large, real-world group of patients. We showed that the progression-free survival (PFS) in patients treated with T-DM1 after pertuzumab was 3.5 months. T-DM1 was mainly administered second-line after pertuzumab. The PFS in higher therapy lines appears to be shorter than in second-line ones. In summary, this study provides evidence that T-DM1 has clinically reasonable activity after prior pertuzumab treatment, with a median PFS period of approximately 3–4 months. It appears to be recommendable to administer T-DM1 in earlier therapeutic lines.The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8–7.8); in second-line treatment, 7.7 months (95% CI: 2.8–11.0); in third-line, 3.4 months (95% CI: 2.3–not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2–NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.

Highlights

Anti-human epidermal growth factor receptor 2 (HER2) treatments have been integrated very successfully into the treatment of patients with HER2-positive breast cancer (BC), since the discovery that HER2 amplifications have a major impact on the prognosis in BC patients [1]
progression-free survival (PFS) = 7.7 months; 95% confidence intervals (CIs): 2.8 to 11.0) than more heavily pretreated patients (Figure 2)
Cancers 2020, 12, x longer PFS than more heavily pretreated patients

Summary

Introduction

Anti-human epidermal growth factor receptor 2 (HER2) treatments have been integrated very successfully into the treatment of patients with HER2-positive breast cancer (BC), since the discovery that HER2 amplifications have a major impact on the prognosis in BC patients [1]. Additional HER2-directed agents, such as the monoclonal antibody pertuzumab and the dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor lapatinib, have been developed to overcome resistance to trastuzumab and provide additional treatment options [2,3,4,5,6,7,8,9,10,11] These treatments have incrementally improved the clinical outcome for patients with early and metastatic disease [12,13,14,15,16,17].

Objectives

Methods

Conclusion