Abstract P4-01-27: Prognosis and treatment landscape of HER2-positive metastatic breast cancer (MBC) before the availability of tucatinib and trastuzumab-deruxtecan: Results from the Austrian AGMT_MBC-Registry
Authors: Gampenrieder Simon P. , Rinnerthaler Gabriel , Tinchon Christoph , Petzer Andreas , Balic Marija , Heibl Sonja , Sandholzer Margit , Zabernigg August F. , Egle Daniel , Hager Christopher , Pichler Petra , Roitner Florian , Andel Johannes , Strasser-Weippl Kathrin , Knauer Michael , Hubalek Michael , Singer Christian F. , Greil Richard 
Published: March 2023

Abstract
Background: New anti-HER2 drugs such as tucatinib and trastuzumab deruxtecan (T-DXd) have shown to improve survival of HER2+ MBC in clinical phase III trials. To allow a future confirmation of this survival advantage in real world, we evaluated the prognosis of HER2+ MBC patients before the availability of tucatinib and T-DXd in Austria. Furthermore, we analyzed the treatment landscape and the drop-out rate between subsequent lines of therapy as documented in the MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT).
Patients and methods: The AGMT-MBC-Registry is a multicenter nationwide ongoing retrospective and prospective registry for MBC patients in Austria. In this analysis, patients with known HER2 status, available survival data, at least one treatment line and diagnosis of metastatic disease after 01/04/2013 (pertuzumab available) were included. Follow-up was censored at Dec 31, 2020, when tucatinib und T-DXd became available.
Results: As of 04/05/2022, 2,235 patients have been included in the registry. Out of 2,000 evaluable patients, 362 (18.1%) were HER2+, of which 171 (47.2%) fulfilled the inclusion criteria. Out of them 69.0% were hormone-receptor positive. In patients with metachronous metastatic disease (53.2%), 61.5% had received trastuzumab-based treatment for early breast cancer. Median overall survival (OS) for all patients was 50.1 months (95%CI 40.7-73.0), and 66.1 months (95%CI 50.1-NA) for those who received a pertuzumab combination as first-line treatment. The drop-out rate from 1st- to 5th-line was 26.9%, 24.4%, 28.3% and 36.7%, respectively. This yields an estimated percentage of patients that received at least 3, 4, and 5 treatment lines for advanced disease of 55.2%, 39.6% and 25.1%, respectively. In first line, 50.9% received trastuzumab plus pertuzumab and 11.1% T- DM1. In second line, 38.9% were treated with T-DM1 and 35.6% with trastuzumab-based chemotherapy or endocrine therapy. In third line, 11.3%, 17.0% and 49.1% received T-DM1, lapatinib-based and trastuzumab-based therapy, respectively. Outcomes according to treatment line are shown in Table 1.
Conclusion: Median overall survival of HER2+ MBC in Austria who received a pertuzumab combination treatment is comparable to the results reported in the registration CLEOPATRA trial. In this analysis, only ~40% of patients are estimated to receive more than three treatment lines and treatment benefit diminished from line to line. This underlines the importance of investigating and ultimately using the most effective compounds in early treatment lines in order to allow more patients to benefit from these life prolonging drugs.
Table 1: Outcome according to treatment line
Citation Format: Simon P. Gampenrieder, Gabriel Rinnerthaler, Christoph Tinchon, Andreas Petzer, Marija Balic, Sonja Heibl, Margit Sandholzer, August F. Zabernigg, Daniel Egle, Christopher Hager, Petra Pichler, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Michael Knauer, Michael Hubalek, Christian F. Singer, Richard Greil. Prognosis and treatment landscape of HER2-positive metastatic breast cancer (MBC) before the availability of tucatinib and trastuzumab-deruxtecan: Results from the Austrian AGMT_MBC-Registry [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-27.