Učinkovitost in varnost zdravljenja s trastuzumab derukstekanom
Efficacy and safety of trastuzumab deruxtecan therapy
analysis of real-world data
DOI:
https://doi.org/10.25670/oi2024-015onKeywords:
breast cancer, HER2, antibody-drug conjugate, trastuzumab deruxtecanAbstract
Nova generacija zdravil, ki se imenuje konjugat protitelesa in zdravila (ADC), trenutno predstavlja eno najučinkovitejših zdravil pri zdravljenju raka. Usmerjena je proti specifični tarči (antigenu), selektivno izraženi na tumorski celici, po vezavi nanjo sledi tarčna znotrajcelična dostava citostatika, ki povzroči celično smrt. Pri razsejanem raku dojk je ADC z imenom trastuzumab derukstekan (T-DXd) pokazal izjemno učinkovitost v več raziskavah pod imenom DESTINY. Naprej so bili na voljo podatki pri razsejanem HER2+ raku dojk, kasneje še pri drugih HER2+ solidnih rakih ter nato še pri raku dojk z nizko izraženostjo HER2. V prispevku predstavljamo prve podatke o učinkovitosti in varnosti T-DXd v Sloveniji. V retrospektivno raziskavo smo vključili bolnike, zdravljene na Onkološkem inštitutu Ljubljana od novembra 2021 do aprila 2024. Ugotavljamo dobre odgovore na zdravljenje (objektivni odgovor 59 % pri HER2+ raku dojk, 38 % pri drugih HER2+ solidnih rakih ter 33 % pri nizkem izražanju HER2). Po kratkem srednjem času spremljanja 8,8 (95 % IZ 0,8–33,3) meseca je preživetje brez progresa v realnem svetu (rwPFS) 13 mesecev pri HER2+ raku dojk, 5,8 meseca pri raku dojk z nizko izraženostjo HER2 in 7,7 meseca pri ostalih solidnih HER2+ ali HER2 mutiranih rakih. Varnostni profil je v skladu s poročili v registracijskih raziskavah, razen za pnevmonitis, ki smo ga beležili v bistveno nižjem odstotku (le 1 %). Zaključimo lahko, da je kljub poznim linijam zdravljenja in heterogeni populaciji delež odgovorov na T-DXd visok, ocena rwPFS pa je ob kratkem času spremljanja še nezanesljiva.
Abstract (Eng)
Antibody-drug conjugates (ADCs) are a new generation of drugs that currently represent one of the most effective treatment options for cancer. ADCs target a specific target (antigen) that is selectively expressed on a tumour cell. Binding of ADCs to a tumour cell results in targeted intracellular delivery of cytotoxic drugs which causes cell death. An ADC called trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in several clinical trials called DESTINY. Initial data were available for patients with metastatic HER2-positive breast cancer, followed by data on other HER2-positive solid cancers and breast cancer with low HER2 expression. In this article, we present the first data on the efficacy and safety of T-DXd in Slovenia. We conducted a retrospective study of patients treated with T-DXd at the Institute of Oncology Ljubljana from November 2021 to April 2024. We observed good responses to treatment (objective response 59% in HER2-positive breast cancer, 38% in other HER2-positive solid cancers and 33% in breast cancer with low HER2 expression). After a short median follow-up of 8.8 (95% CI 0.8-33.3) months, real world progression-free survival (rwPFS) was 13 months in HER2-positive breast cancer, 5.8 months in HER2-low breast cancer, and 7.7 months in other HER2 positive or HER2-mutated solid cancers. The safety profile was consistent with that reported in the registration studies, with the exception of pneumonitis, which was reported in a much lower percentage (only 1%). We can conclude that the response rate to T-DXd is high despite the late treatment lines and the heterogeneous population, while rwPFS assessment is unreliable due to the short observation period.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Nina Privšek, Simona Borštnar, Cvetka Grašič Kuhar

This work is licensed under a Creative Commons Attribution 4.0 International License.
The journal is published under the terms of the Creative Commons Attribution License CC-BY 4.0. The authors retain the copyright to their work without any restrictions whatsoever.
This journal is an open-access journal, meaning that all of its contents are freely accessible without any charge to the user or their institution. In accordance with the Budapest Open Access Initiative (BOAI) definition of open access, users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking for prior permission from the publisher or the author, provided the authors and the journal are appropriately credited.